The common leaching solutions in single stage soil extraction analysis [36, 42].
\r\n\t
",isbn:"978-1-80356-951-2",printIsbn:"978-1-80356-950-5",pdfIsbn:"978-1-80356-952-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"bb6fc82b35ad2c63618a9bc15aeb61ce",bookSignature:"Dr. Kim Ho Yeap and Dr. Magdalene Goh Wan Ching",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11948.jpg",keywords:"MOSFET, CMOS, OFET, JFET, FinFET, Integrated Circuit (IC), Oxidation, Metallization, Semiconductor, Silicon (Si), Gallium Arsenide (GaAs), Silicon Carbide (SiC)",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A researcher in the fields of microelectronics and electromagnetics. Member of IEEE, IET, IEM.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"24699",title:"Dr.",name:"Kim Ho",middleName:null,surname:"Yeap",slug:"kim-ho-yeap",fullName:"Kim Ho Yeap",profilePictureURL:"https://mts.intechopen.com/storage/users/24699/images/system/24699.jpg",biography:"Kim Ho Yeap is an Associate Professor at Universiti Tunku Abdul Rahman, Malaysia. He is an IEEE senior member, a Professional Engineer registered with the Board of Engineers, Malaysia,a Chartered Engineer registered with the UK Engineering Council, and an ASEAN Chartered Professional Engineer (ACPE). He received his BEng (Hons) Electrical and Electronics Engineering from Universiti Teknologi Petronas in 2004, his MSc in microelectronics from Universiti Kebangsaan Malaysia in 2005, and his PhD from Universiti Tunku Abdul Rahman in 2011. In 2008 and 2015, respectively, Dr. Yeap underwent research attachment at the University of Oxford (UK) and Nippon Institute of Technology (Japan). Dr. Yeap is the external examiner and external course assessor of Wawasan Open University. He is also the Editor in Chief of the i-manager’s Journal on Digital Signal Processing. He has also been a guest editor for the Journal of Applied Environmental and Biological Sciences and Journal of Fundamental and Applied Sciences. Dr. Yeap has been given the university teaching excellence award, and 22 research grants. He has published more than 100 research articles (including refereed journal papers, conference proceedings, books, and book chapters). Prior to joining the academic industry, Dr. Yeap worked in Intel corporation in the pre-silicon validation group. He was awarded 4 Kudos awards by Intel for his contributions in the design and verification of the microchip’s design for testability (DFT) features.",institutionString:"Universiti Tunku Abdul Rahman",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universiti Tunku Abdul Rahman",institutionURL:null,country:{name:"Malaysia"}}}],coeditorOne:{id:"454196",title:"Dr.",name:"Magdalene",middleName:null,surname:"Goh Wan Ching",slug:"magdalene-goh-wan-ching",fullName:"Magdalene Goh Wan Ching",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Dr Magdalene Goh Wan Ching\r\nDesignation: Senior lecturer\r\nQualifications: Diploma in Electrical & Electronics Engineering (Inti College), BEng in Electrical\r\nEngineering & Electronics (University of Liverpool, UK), PhD in Solid State\r\nDevice Physics & RF Transistors Design (University of Liverpool, UK)\r\n\r\nProfessional Body\r\nMemberships:\r\n\r\nInaugural Senior Member, International Engineering & Technology Institute\r\n(IETI), Hong Kong\r\n\r\nBiodata: Dr. Magdalene Goh obtained her Diploma in Electrical & Electronics Engineering\r\nfrom Inti College before leaving for the UK to pursue her BEng in Electrical\r\nEngineering & Electronics and later on, her PhD. Prior to joining the academia,\r\nshe has worked for a few years in the industry in the areas of semiconductor\r\nprocess technology, silicon wafer characterizations, mask layout design,\r\nanalogue circuits design and design for testability (DFT). While in the academic,\r\nshe had served as a judge for Innovate Malaysia undergraduate final year\r\nprojects competition from 2012 - 2015. She had served as an external examiner\r\nfor a PhD candidate from VIT University, India in 2013, and an external examiner\r\nfor SEGi College Penang from 2014 – 2018. She has been actively involved with\r\nthe Penang Science Cluster in their radio telescope team since 2014, where she\r\nworks with a team of volunteers (from both academia and the industry in\r\nPenang) to create curricula in radio astronomy, for the purpose of introducing the\r\nconcepts of radio astronomy and radio telescopes to both school pupils and\r\ncollege students. She has been a member of the Astronomical Society of\r\nPenang since 2016.\r\n\r\nCourse Development\r\nExperience:\r\n\r\nSince joining WOU, Dr. Goh has developed eight courses, namely Control\r\nSystems, Microprocessors, Digital Communications, Microelectronics, VLSI\r\nDesign, Process Control & Instrumentation, Power Electronics & Drives and\r\nElectrical Power & Drives.\r\n\r\nResearch Interest: Dr. Goh’s research interests are in the areas of semiconductor physics and\r\nelectromagnetics. She also has strong interest in the field of astronomy and is\r\nworking with a group of volunteers to promote astronomy education in the\r\nsecondary schools in Penang. She had also worked with some interns on the\r\nradio telescope project at the Penang Science Cluster.\r\n\r\nResearch Projects and\r\nConsultancy Work:\r\nSelected Publications: Design of Radio Frequency Metal-Insulator-Metal (MIM) Capacitors. \r\n\r\nExperimental Investigation on Thermoelectric Generator for Battery - Charger\r\nBased Oven.\r\nAnalyzing the Physics of Radio Telescopes and Radio Astronomy (book\r\nchapters).\r\n\r\nConferences,\r\nSeminars and\r\nWorkshops:\r\n\r\nDr. Goh was appointed as one of the Technical Committee Member for the\r\nVirtual Conference on Electronics and Communication: Loading Intelligence on\r\nFuture Electronics (October 2020).\r\n\r\nHonorary\r\nAppointments and\r\nAwards:\r\n\r\nDr. Goh is a reviewer of the following journals:-\r\n1. Microwave and Optical Technology Letters.\r\n2. Journal of Electrical Engineering.\r\n3. Journal on Digital Signal Processing.\r\n\r\nOfficial\r\n\r\nDr. Magdalene Goh Wan Ching\r\nSenior Lecturer & Programme Coordinator of Bachelor of Technology in\r\n\r\nCorrespondence\r\nAddress:\r\n\r\nElectronics,\r\nSchool of Science & Technology\r\nWawasan Open University\r\n54, Jalan Sultan Ahmad Shah,\r\n10050 Penang\r\n\r\nEmail Address: magdalenegoh@wou.edu.my\r\nPersonal Homepage\r\n(optional):\r\n\r\nBTEL facebook page:\r\nhttps://www.facebook.com/groups/238200129533176/",institutionString:"Technology Wawasan Open University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"10198",title:"Response Surface Methodology in Engineering Science",subtitle:null,isOpenForSubmission:!1,hash:"1942bec30d40572f519327ca7a6d7aae",slug:"response-surface-methodology-in-engineering-science",bookSignature:"Palanikumar Kayaroganam",coverURL:"https://cdn.intechopen.com/books/images_new/10198.jpg",editedByType:"Edited by",editors:[{id:"321730",title:"Prof.",name:"Palanikumar",surname:"Kayaroganam",slug:"palanikumar-kayaroganam",fullName:"Palanikumar Kayaroganam"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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The activity of a particular radioactive substance is characterized by the constant decay rate and the half-life (t1/2—time taken for the activity of a given quantity of a radioactive substance to decay to half of its initial value), and it is a general rule of thumb that ten half-lives are required for each radioisotope to be eliminated [2]. Since the half-lives of various nuclei vary from seconds to billions of years [3], the time required for their total decay significantly differ as well.
\nSome radionuclides occur naturally in the environment, and their presence is either cosmogenic or terrestrial. The 3H, 7,10Be, 14C, 26Al, and 39Ar are the main radionuclides produced after the interaction of atmospheric gases with cosmic rays. On the other hand, the rocks, minerals, and consequently the soil, contain naturally occurring radioactive materials (NORM), characterized by a long half-life periods [3]. The most important terrestrial radionuclides are 238U and 232Th decay series, as well as 40K. The world average values for soil activity coming from 226Ra, 232Th, and 40K are 32 Bq/kg, 45 Bq/kg, and 420 Bq/kg, respectively [4].
\nThe term radioactive contamination indicates the unintended or undesirable presence of radioactive substances on the surfaces or within solids, liquids, gases, or biota [5]. The origin of NORM is related to the formation of the planet; thus, their presence cannot be referred to as contamination. On the other hand, anthropogenic activities, related to the development of nuclear energy and its versatile use, have become important source of pollution. Since the middle of the last century, the radioactive contamination have appeared through the discharge of man-made radionuclides, making the ionizing radiation one of the important ecological factors, in line with other types of soil degradation (physical, chemical, and biological) [6]. Even though the radioactive contamination of the environment is relatively rare, it requires a great attention because of extreme degrading effects of ionizing radiation on living tissues. The adverse effects are in correlation with the quantity of absorbed energy, the penetrating power of the radiation, the duration of the exposure, as well as with the reproduction rate of the cells of a certain tissue [3].
\nIn terrestrial ecosystems, soil corresponds to the major receiving pool of emitted radionuclides. Given that the nutrient cycles and the flow of energy present links between the abiotic and biotic components of the ecosystem, soils contaminated with radionuclides lose their ability to produce good quality agricultural crops and thus can be classified as degraded [6]. The issues related to the degradation of radioactively contaminated soils are being considered as an exceptional type of chemical contamination, with the additional, specific features related to the ionizing radiation.
\nThe transport and fate of radionuclides in the soil are governed by a number of factors and the effects of their interactions; therefore, the detection and comprehension of the retention mechanisms are of great importance for the selection, development, and application of appropriate remediation technologies. In this chapter, the following topics were summarized and discussed: (i) sources of soil contamination by radioactive pollutants, (ii) interactions with soils constituents, (iii) factors influencing radionuclide mobility in the soil (iv) methods for the assessment of radionuclide mobility in the soil, and (v) the remediation strategies based on the increase or decrease of pollutant mobility.
\nContamination of the soil with the radioactive pollutants is an important origin of hazard for the environmental and health safety, as well as for the economy. Exploitation of the nuclear energy is a key source of pollution. Radiation can enter and affect the environment at any of the stages of the nuclear fuel cycle, starting with the excavation and processing of uranium ore, over production and recycling of the nuclear fuels, to the processing and disposal of radioactive wastes. The average uranium concentration in the earth crust is 2.8 mg/kg [7]. This radionuclide is contained with variable concentrations in the range of oxide, silicate, arsenate, vanadate, and phosphate minerals. Ores, processed by conventional uranium production methods, vary from reach (>20%, Canada) to very poor (0.01%, Namibia) [8]. Uranium is extracted from the ore matrix by hydrometallurgical process, and the final product, (the so-called yellowcake), used in the following steps of the nuclear fuel production typically contain 75–85% U3O8. Studies of the effect of uranium production process onto environmental pollution and the potential health risks have revealed elevated activities at cites around ore processing facilities and around old mines, in particular [9, 10]. Nowadays, almost half of world-wide uranium mining, and most of the mining in the USA, Kazakhstan, and Uzbekistan, was conducted by
Any material that is radioactive itself or is contaminated by radioactivity at levels greater than the quantities established by the competent authorities, and which cannot be of further use, is characterized as—radioactive waste. Within civil society, this kind of waste arises mainly from nuclear power production, but also from a variety of industries, medicine, agriculture, research, and education and other activities in which radioisotopes are used [13]. The radioactive wastes are being classified based on the level of radioactivity (low, medium, and high) and the half-lives of the isotopes with predominant activity [14]. In the short-lived waste, predominant activity is defined by radionuclides with t1//2 < 30 years, whereas the long-lived wastes are characterized by isotopes with t1/2 > 30 years.
\nProcessing of radioactive waste may result in an accidental release of the radionuclides during characterization, segregation, transportation, treatment, and disposal. By the review of the inventory of fission products important in the case of accidental releases, it can be concluded that 89Sr, 90Sr/90Y, 91Sr, 92Sr, 95Zr, 97Zr, 103Ru/103mRh, 105Rh, 129mTe/l29Te, 131mTe/131Te, 132Te, 131–135J, 140Ba/140La, 134Ce, 144Ce/144Pr are important pollutants at the reactor stage; 90Sr, 125mTe/129Te, 131I, 134Cs, 137Cs may be released during fuel element transport; 90Sr, 95Zr/95Nb, 106Ru, 131I, 137Cs, 144Ce/144Pr, and actinides are important at the fuel reprocessing stage; 90Sr, 106Ru, 137Cs, and 144Ce/144Pr contamination may occur during fission product solidification, whereas leaching from the final disposal may result in soil contamination with 90Sr, 137Cs, and actinides [15]. In addition to fission products, several corrosion products may become significant soil pollutants. Namely, during nuclear reactor operation, most metallic surfaces oxidize and form a layer of corrosion film rich in oxides of structural elements. This layer is exposed to high pressures and temperatures, where radionuclides are generated under the neutron activation [16]. Depending on the composition of the reactor materials and their trace elements, reactor type and design, thermal power, years of irradiation and shutdown period, the corrosion products and their relative proportions are different. The products of steel corrosion are 55Fe, 59Ni, 63Ni, 94Nb, 60Co, 39Ar, 54Mn, with the 60Co and 55Fe being the most important in the first 10 years following the closure of a reactor, and 63Ni, 94Nb, 108Ag in the next 50 years. Reinforced concrete’s corrosion products are 3H, 14C, 41Ca, 55Fe, 60Co, 152,154Eu, whereas 3H, 14C, 152,154Eu originates from graphite. Considering these two groups of materials, 3H becomes the most prominent after 10 years, and 14C, 41Ca, 152,154Eu after 50 years from the reactor shut-down. Taking into account both fission and corrosion products, 10–20 years after the reactor shutdown the most abundant radionuclides in contamination residues generally include 3H, 60Co,55Fe, and 137Cs, whereas in the period 20–30 years, 63Ni, 137Cs, 60Co, and 90Sr generally prevail [16].
\nAnother key source of soil contamination with radionuclides is nuclear weapons tests, particularly atmospheric, which have started in 1945 in the USA [17]. In the period 1945–1980, the power of USA atmospheric tests (428 megatons) was approximately equivalent of the size of 29,000 Hiroshima bombs [17]. Finally, in 1990, thanks to the moratorium signed by SSSR, UK and USA, nuclear testing was stopped. Atmospheric detonations produce radioactive debris of different particle size, which are partitioned in the tropo- and stratosphere and my precipitate over a period of a few minutes to 1 year, or longer [18]. The concern is especially focused onto released Pu isotopes, due to the high biological toxicity and long half-lives of its relevant isotopes (e.g., 24.2 × 103, 373 × 103, 81 × 106 years, respectively, for 239Pu, 242Pu, and 244Pu) [19]. Furthermore, 137Cs, 90Sr, 241Am, and 131I are the released radioactive isotopes with major impact on the environment and irradiation of the human body [20]. The mentioned isotopes were predominantly found in most of the nuclear test sites worldwide, especially in western US soil [21, 22].
\nNuclear accident are the events that led to significant consequences to people, the environment or the facility, such as the ones in Chernobyl (Ukraine, 1986) and Fukushima (Japan, 2011). These two events caused global contamination of the environment, including air, water, soil, and living organisms. Huge amounts of radioactive elements especially 131I, 137Cs, 90Sr and the sum activity of 239Pu and 240Pu were dispersed into environment [23]. Some 40% of Europe has been exposed to Chernobyl’s 137Cs at a level 4–40 kBq/m2 [24]. The size of the disaster can be illustrated by the fact that the maximum radioactive contamination in the soil in the 1993 was found to be 3500 times higher than the level before Chernobyl accident.
\nApart from uranium mining and related fuel cycle activities, the industrial sectors which generate technologically enhanced naturally occurring radioactive materials (TENORM) include the following: mining and combustion of coal, the oil and gas production, metal mining and smelting, production of mineral sands (rare earth minerals, titanium, and zirconium), phosphate fertilizer industry, building industry, and recycling [25–27]. The dose of radiation coming from primordial radionuclides (40K, 232Th, 235U, 238U, and the members of decay series), which are normally found in natural minerals and ores (uranium ore, coal, phosphate rock, monazite, bauxite, etc.), can be elevated in their by-products and wastes such as phosphogypsum, fly ash, and red mud. Consequently, the releases from non-nuclear industries represent a continuous source of soil contamination with natural radioactive elements, by spreading of dust from rock and solid wastes dump, as well as by the overflow of wastewater from treatment ponds. Furthermore, years of application of phosphate fertilizers enriched with TENORM may become a source of soil contamination. Depending on the contamination level, restriction of land use or the remediation measures may be necessary. Finally, soil contamination may also arise from less common sources such as incidents during use of radioisotopes in medicine, industry, and agriculture [28].
\nAt 160 U.S. Department of Energy (DOE) sites with radioactive contamination, 137Cs, 226Ra, 238U, 238–242Pu, 60Co, 232Th, and 90Sr were detected as the key artificial and natural radionuclides [29].
\nInteractions of contaminants with soil matrix, and their variation with environmental parameters, are essential for radionuclide transport and fate, as well as for the risks to the living organisms and the environment. The uptake of radionuclides by soil can occur through diverse modes of interactions, while at the same time, other mechanisms are responsible for their elimination from the soil matrix (Figure 1). Due to the dynamic nature, heterogeneity and the overall complexity of the soil as a system, studying, understanding, and predicting the radionuclides behavior are the major challenges.
\nFactors influencing radionuclide distribution in the soil include the source term and the release conditions, transport and dispersion mechanisms, and the properties of the ecosystem [30]. Source term (ions, colloids, particles, oxidation states, etc.) influences mobility properties of radionuclides, since the transfer of mobile species in the ecosystem is faster in respect to the transfer of particles. Furthermore, the properties of the particular radionuclide, its chemical form and the reactivity, control the nature of its retention in the soil and the affinity to certain soil constituents.
\nSoil properties are primarily grouped into physical (texture, structure, porosity, water, air, and heat regimen), chemical (chemical and mineralogical composition, pH, microelements, micronutrients, salinity (EC), cation exchange capacity (CEC), organic matter, etc.) and biological (macroflora, macrofauna (rodents, insects, woodlice, mite, snails, millipedes, spiders, worms), microflora (bacteria, actinomycetes, fungi, and algae), and microfauna (nematodes and the protozoa)) [31, 32]. All five basic components of the soil, that is, minerals, water, organic matter, gasses, and the microorganisms, affect the binding and retention of the pollutants to a greater or lesser extent, depending on the pollutant type.
\nThe mechanisms of radionuclide binding and elimination from soil matrix.
The interactions between radionuclide and the soil include physical (reversible) sorption governed by the uncompensated charges on the surface of the soil particles, and the chemical (principally irreversible) sorption through high affinity, specific interactions, and establishment of covalent bonds [33, 34]. The primary minerals in soil, mainly quarts and feldspar, are derived from the parent rock and make up most of the sand and silt fraction. Due to the relatively low specific surface area, their role in contaminant interaction is the smallest, and the attachment occurs through reversible sorption [35]. Secondary minerals, such as clay, result from physical, chemical, and biological weathering processes. Because of the unbalanced charges of structural ions, they are the carriers of permanent surface charge, which in combination with small particle size and large specific surface area make them important matrices for contaminant retention. Furthermore, oxides and (oxy)hydroxides of Fe and Al are abundant in amorphous form, with pH-dependent surface charge. Soil organic matter consists of chains of carbon atoms, containing polar and/or ionized surface functional groups, such as OH– and COOH–. Consequently, clay minerals, Fe, Al-oxides, and organic matter undergo a variety of interactions with contaminants.
\nThe bonds established between the particular radionuclide and the particular soil type can be assessed by different analytical approaches. Chemical reagents of various composition, strength, and selectivity are the most widely used, in the single stage or sequential extraction protocols [30, 36–41]. The aim of such tests was assessment of the transport mechanism in a soil profile and the potential toxicity, with implications to the risks to the biota and the ground water reservoirs. In general, weaker bonds between the pollutant and the soil components signify higher mobility of radionuclide, its increased possibility to reach the plants and soil organisms and to enter into the food chain. However, the mobility and bioavailability of closely related, they cannot be equalized in the interpretation. Bioavailability processes are defined as the physical, chemical, and biological interactions that determine the exposure of plants and animals to chemicals associated with soils and sediments, they incorporate a number of steps and represent the amount of a contaminant that is absorbed following skin contact, ingestion, or inhalation [42]. On the other hand, the bioaccessibility of the contaminant is defined as its fraction soluble in the gastrointestinal tract and available for absorption.
\nReview of the literature shows that a wide spectrum of single-stage extraction methods for soil analysis is in use [36, 42]. Basic groups of reagents include acids, chelating agents, and salts; moreover, reagent concentrations and other experimental conditions are considerably different (Table 1). In contrast to the well-established methods for the determination of soil major nutrients and fertility, the procedures for the extraction of pollutants are not standardized.
\nThe most common chemical reagents | \nCommon concentration ranges (mol/L) | \n|
---|---|---|
Acidic solutions | \nHNO3, HCl, CH3COOH, H2SO4 | \n0.01–2 | \n
Chelating agents | \nEDTA*, DTPA** | \n0.005–0.01 | \n
Salt solutions | \nCaCl2, NaNO3, NH4NO3, AlCl3, BaCl2 | \n0.01–0.1 | \n
Buffered salt solutions | \nNH4CH3COO/CH3COOH (pH 4.8, pH 7) | \n1 | \n
In addition to acidic and salt-containing solutions, the chelating agents are applied, due to their efficiency in extracting potentially bioavailable soluble complexes of radionuclides with organic matter. The results of leaching tests represent a rough measure of mobility, as the actual mobility in the field depends also on moisture, leaching, root uptake of nutrients, activity of microorganism, and many additional factors. Furthermore, the agreement between chemically extracted and fractions available to biota should be confirmed empirically, for wide variety of contaminated samples [43].
\nSpeciation analysis is conducted for the identification and determination of the different chemical and physical forms of elements in the soil matrix [44]. The distribution of radionuclides is related to their affinity towards certain soil components; thus, they can exist as a free ions or in the form of soluble complex ions in interstitial solution; as exchangeable ions attached to the soil surface, they can be associated with soil organic fractions, occluded, or co-precipitated with metal oxides, carbonates, phosphates, or other secondary minerals, and incorporated inside the crystal lattices of primary minerals.
\nThe sequential extraction protocols were primarily developed for the determination of the distribution of stable macro- and micro-constituents of the soil. Identification of the mobility and availability of trace elements, both the essential ones and the pollutants, is particularly important for the improvement and protection of the plant development and growth, and for the health of the ecosystem as a whole. Different sequential extraction methods have been proposed to separate the fractions of elements from various pools. The so-called Tessier method [44] and the method proposed by the European Community Bureau of Reference—the BCR method [45], are the two commonly used protocols, while many others are based on their modifications. Additionally, a modified version of Tessier’s method was proposed at the Speciation Workshop organized by the National Institute of Standards and Technology (NIST), in order to optimize the protocol of soil extraction and select operationally defined fractions which can be separated by appropriate chemical reagents [46].
\nEvaluation of element distribution in soils by the sequential extraction is based on the assumption that mobility decrease with each extraction step (Figure 2), implying that under natural conditions elements in water soluble and exchangeable fractions are the most mobile and bioavailable, whereas those in residual fractions are the most tightly bound.
\nCommon phases in sequential extractions based on Tessier’s protocol [
The lack of the standardized procedure for the determination of pollutant mobility makes the interpretation and the comparability of the results difficult. In addition, the effect of the reagents may be questionable. For example, extracting solution having pH 5, used for the dissolution of carbonate phase, may also sequester ions specifically sorbed onto surface of other soil constituents [47]. The fractions of pollutants are defined only operationally; thus, instead of being associated with the terms
where the mobile species include the fraction such as H2O and CH3COONH4 extractable and that taken up by vegetation from the same site.
\nAlthough none of the methods can provide the absolute quantities associated to the specific component of the soil, such analyses represent valuable tool in elements mobility and availability assessment, and for tracking the effectiveness of soil remediation actions. Experiences achieved by practicing single and sequential chemical extractions reveal advantages of these methods but also a need for further research and developments due to increasing soil contamination which requires fast, reliable, and cost-effective assessment.
\nIn addition to extraction methods, studies of the radionuclide retention mechanism can be complemented by the determination of the type of the surface complexes, identification of the radionuclide incorporation in the crystal lattice of existing minerals, or the formation of new solid phases, etc., for which instrumental techniques are applied (X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), scanning electron microscopy with energy dispersive X-ray spectroscopy (
Furthermore, bioassay tests involving plants, animals, and microorganisms, are valuable for the analysis of radionuclide mobility and bioavailability [52]. Soil-to-plant transfer factors (TF) have been widely used in radioecology, in order to quantify the availability of soil radionuclides for plant uptake [36]:\n
As soil-to-plant transfer considerably differs between different plant species and the seasons, this method also gives crude estimations of potential radionuclide bioavailability. In spite of limitations, transfer factors are currently accepted as the most practical way of describing plant uptake. Also, several in vitro methods have been developed for the prediction of the relative bioavailablity of the contaminants, using physiologically based fractionation schemes [42, 53]. These methodologies mimic key processes that take place in vivo, such as contaminant dissolution, and after establishing a strong correlation between the in vivo and in vitro results, these methods have a potential to overcome the time and expense limitations of in vivo studies.
\nA capacity of the soil itself to immobilize radionuclide is the main factor controlling activity concentrations available to biota, and it operates in conjunction with the numerous external factors. Soil texture and structure, mineral composition, organic components, redox potential (Eh) and pH, as well as rainfall, climate changes, and soil management, are recognized as important for radionuclide mobility [54]. The pH of the soil, cation exchange capacity (CEC), and total organic carbon (TOC) are the physicochemical characteristic most often correlated with the distribution of the radionuclides [40]. Alkaline soils are characterized by the presence of carbonates and have a high saturation of base cations (K+, Ca2+, Mg2+, and Na+), whereas acidity in soils comes from H+ and Al3+ ions in the soil solution and sorbed to soil surfaces. The surface charge of minerals is a major contributor to soils CEC and influences the soil’s ability to retain important nutrients and the pollutants. The texture of a soil is based on the relative content of sand (0.05–2.00 mm), silt (0.002–0.05 mm), and clay (<0.002 mm) fraction. Due to the finest granulation, clays minerals exhibit the largest surface area, important for soil chemistry and CEC, but also for water-holding capacity important for transporting nutrients and pollutants to soil organisms and plants. In addition, soil organic matter significantly contributes to the soil CEC and to the water-holding capacity.
\nBased on the literature data, the influence of soil properties and other condition on the mobility of some important pollutants is given in Table 2.
\nRadionuclide | \n||||
---|---|---|---|---|
\n | Cs | \nSr, Ra | \nU, Pu | \nI | \n
Chemical form | \nCs+ | \nSr2+ | \nPuO22+, Pu(NO3)3+ | \nI2, I−, IO3− CH3I | \n
\n | \n | Mobility | \n\n | \n |
pH decrease | \nIncrease | \nIncrease | \nIncrease | \n\n |
Clay content decrease | \nIncrease | \nIncrease | \nIncrease | \n\n |
Sand content decrease | \nDecrease | \nDecrease | \nDecrease | \nIncrease | \n
Humus content low | \nNot clear | \nDecrease | \nDecrease | \n\n |
CEC decrease | \nIncrease | \nIncrease | \nIncrease | \n\n |
Aging | \nDecrease | \nWeak effect | \nDecrease | \n\n |
Apart from soil type, different sources of variability may influence the fractionation patterns and cause the shift from less available to more available fractions, or vice versa. Generally, the increase of contaminant concentration not only increases the overall activity in the soil but also leads to redistribution from the less to the more available fractions [57]. Radioactive contamination introduces new elements into the ecosystem and, in distinction from the transport of stable elements and NORM, transfer of contaminants through the trophic chains occurs under non-equilibrium conditions. Consequently, ageing affects a decrease in the chemical mobility and biological availability of most of the radioactive pollutants [58]. The ageing process actually involves a set of reactions related to the enhancement of radionuclide sorption and fixation by the soil solid phase (i.e., the precipitation or penetration into the crystalline lattices of different mineral constituents. Aging exhibits a different effect on different ions. Increased contact times (months to years) were found to affect gradual reduction of Co2+ ions mobility [57, 59]. Time-dependent studies on the variation in Cs+ bioavailability have revealed that over years, a decrease in the labile fraction of 137Cs in soils was correlated with a decrease in soil-to-plant transfer [60]. In contrast, due to low sorption affinity of 90Sr towards soil constituents, impact of aging is very weak considering 90Sr speciation [40]. The behavior of Sr2+ and its uptake by living organisms are controlled by its similarity to calcium; thus, regardless of the soil type, contamination level, and aging time, it was largely found in water-soluble and ion-exchangeable fractions of soil. Seasonal effects may also cause variations in radionuclide mobility, and these effects can be controlled by appropriate sampling plan [57].
\nAs the environmental conditions change, the distribution of pollutant also changes, causing the increase or the decrease in mobility. Knowledge of such dependencies represents the theoretical background for the development of mobilization/immobilization remediation methods. Furthermore, exploration and development of suitable solid and liquid media are fundamental in support of these technologies. Mobilization techniques imply weakening of bonds with the soil constituents provoking desorption, dissolution, and chalation of the pollutant [61, 62]. On the other hand, the general idea of the radionuclide immobilization (stabilization) is to induce chemical reactions, precipitation, and other processes which cause redistribution of the contaminants from more labile to more stable forms [61, 63]. Both principles exhibit certain benefits and drawbacks. Stabilization techniques are usually less expensive and easier to perform in comparison with the alternative processes; however, the total activity concentrations remain in the soil, posing a constraint for the future uses. Otherwise, the techniques based on the pollutant exclusion from the soil matrix represent a permanent solution for the contaminated site. However, transportation, consumption of the chemicals and the energy, and further management of the resulting liquid phase with the extracted pollutants, make these techniques complicated and costly. Remediation activities may also result in some negative effects on the soil properties, including fertility; thus, evaluation of suitable strategies and decision-making process require detailed knowledge of all these aspects.
\nChemical extraction is the technique that stimulates the redistribution of contaminants from the solid phase to the solution, in order to selectively remove the contamination, or to enhance its physical separation [61, 64]. The contaminated soil is excavated and treated off-site. After the treatment, the soil is returned to its original location, while the activity remains concentrated in the extraction medium. The extract is subsequently treated to precipitate the activity and return the leaching reagents to the process. Otherwise, the extracting solutions can be implemented
Radionuclides in the soil can be re-mobilized by four principal means [66]: (1) changes in the acidity, (2) changes in the ionic strength of the solution, (3) changes in the soil redox potential, and (4) formation of soluble complexes. To extract the pollutants, acids operate on the ion-exchange principle, and by dissolution of soluble soil components. Highly concentrated solutions of inorganic salts displace the radionuclides from ion-exchangeable sites by mass action, and if implemented at low pH this effect is combined with the effects of acid leaching. Chelating agents solubilize metals through complexation, while redox manipulation aims to enhance solubilization by the change of valence and thus chemical properties. The most common chemical agents are inorganic salts (CaCl2, NaCl), mineral acids (HCl, H2SO4, HNO3), and complexing agents (EDTA, DTPA, oxalate, citrate, etc.) [61, 65, 67].
\nSelection of the proper chemical extracting reagent is influenced primarily by the radionuclide type, its speciation pattern and the characteristics of the soil. Pollutants that are majorly accumulated in ion-exchangeable, carbonate, and Fe, Mn oxide fractions are the most suited for the removal by chemical leaching [68]. The soils characterized by low pH, low content of clay, and humic substances are the promising candidates for such treatments [61].
\nIn order to extract the target metal from the soil environment, the strength of the radionuclide-chelating agent complex must overcome the strength of the bonds keeping raionuclide attached to the soil surface. The efficiency of EDTA is superior, and it is usually applied at pH 4–8, as the EDTA-complexes can be re-adsorbed on soil surface sites at lower pH [69]. In addition to the high price, selectivity of EDTA towards target radionuclides, its recovery and reuse are the major drawbacks. Furthermore, its low degradability can be a persistent problem after the soil treatment. Thus provided that they enable efficient removals of pollutants, and acidic and salt-containing solutions are more acceptable due to lower environmental impact and the ease of regeneration.
\nIn the comprehensive investigation of appropriate chelating agent for the extraction of various radionuclides, the regressive empirical predictive model was developed as a selection tool [62]. Using as the input variables, the properties of the chelators, various stability constants, radionuclide distribution, and the soil properties (mineralogical composition, pH, clay content, CEC, etc.), the following adequate chelator for target radionuclide were proposed: EDTA, DTPA, and nitrilotris(methylene)triphosphonic acid (NTTA) for Ba and Ra; 2-aminoethanethiol, EDTA, DTPA, thiobis(ethylenenitrilo)tetraaceticacid (TEDTA), and N-2-acetamidoiminodiacedicacid (ADA) for Pb and Th; whereas iminodiaceticacid (IDA), nitrilotriaceticacid (NTA), and ethylenediiminodiacetic acid (EDDA) were suggested for the extraction of Pu and U.
\nSelective removal of 137Cs and 90Sr from soil poses a problem, due to the lack of suitable complexing agents [61]. Although certain crown ethers form complexes with these cations, due to the toxicity and high cost of such agents, large-scale agricultural applications are impractical. Solutions of HCl, CaCl2, EDTA, tartaric, and citric acid, with different concentrations of reagents, were applied to soil artificially contaminated with Sr2+ and Co2+ ions [39]. Due to its predominant association with ion-exchangeable fraction, Sr2+ ions were efficiently desorbed using Ca2+ or acidic solutions. On the other hand, Co2+, which was largely distributed between carbonate and Fe, Mn-oxide fractions, was leached most efficiently by complexing agents.
\nChemical extraction processes have a large potential in the rehabilitation of the soil that have undergone radioactive contamination and their effectiveness can be additionally improved by optimizing reagent type and concentration, soil/solution ratio, pH, contact time, mixing, and other factors.
\nDespite the fact that the main objective of the soil remediation was the removal of the maximum amount of pollution, the major obstacles for the routine application of such an approach are the processing and the disposal of the radioactive waste resulting from the soil clean-up [70]. The insufficient storage capacities, especially for waste classified as low level, long-lived, are significant and global problem. As a consequence, immobilization treatments are being rapidly developed, with main goals to reduce the risk of exposure and uptake by biota, and the risk of the spread of contamination.
\nThe application of soil amendments is performed on site (
As the most of the radionuclides in soil exist in the cationic form, increase in pH, clay content, and CEC lead to an increase in pollutant stability (Table 2). Consequently, water-soluble and water-insoluble amendments are applied, with a role to modify the environmental conditions in favor of radionuclide stabilization or to directly interact with the contaminants (or both).
\nIn order to raise pH and lower pollutants accessibility to plants, the materials traditionally applied to soil are carbonates, lime, and phosphates [72]. Other soil amendments that are currently in use or are under consideration and verification have been modeled after stabilization or encapsulation agents (such as cement) used for safe disposal of radioactive and hazardous wastes. Various forms of aluminosilicates, phosphates, carbonates, silicates, oxides, and hydroxides were largely investigated [65, 72]. In general, solid matrices that have shown superior immobilization potential towards radioactive ions in aqueous solutions are suitable for testing in the contaminated soil. Based on the numerous investigations of the sorption affinities and capacities toward variety of radioactive pollutants, the most prominent groups of materials are aluminosilicates [73–80] and phosphates [81–89]. The main operating mechanisms are quite different for these two groups: while aluminosilicate addition to soil increases the number of sorption sites, phosphate materials, mainly from the apatite group, act through several removal mechanisms (ion-exchange, formation of specific surface complexes, and structural incorporation of pollutants by co-precipitation and dissolution/precipitation processes).
\nAluminosilicates, primarily clay minerals, and zeolites are inorganic ion-exchangers with high surface area, which have been conventionally used for water treatment processes, for the treatment of liquid nuclear waste, and for the protection against nuclear waste leaking [79–90]. Natural zeolites are the framework aluminosilicates, with variable porosity due to which they can selectively capture the ions having an appropriate radius. Zeolites are excellent sorbents of fission products that otherwise exhibit very low affinity for sorption on solid surfaces (such as Cs and Sr isotopes [78, 80]. Clay minerals (montmorillonite, vermiculite) are layered aluminosilicates, in which ion-exchange is typically associated with cations situated in clay mineral interlayers [72]. The stabilization of Cs+ and Sr2+ contamination in the sandy soils was tested using different synthetic and natural zeolites [91]. With the addition rate of 1%, the maximum reduction of soil-to-plant transfer factor of 12.5 for Cs+ and 24.5 for Sr2+ions, was observed, as well as the significant changes in cationic composition and pH of the soil. By comparing the effect of various materials onto Sr2+ immobilization in the soil, zeolite has been identified as the most efficient, followed by bone char, synthetic hydroxyapatite, and phosphate rock [92]. The most of the results have been obtained on the laboratory level or out of small-scale field applications, while in solving the actual problems of soil contamination, applications are generally connected with Chernobyl and Fukushima disasters.
\nThe other promising group of materials is the phosphate group. Among different soluble and sparingly soluble phosphate bearing materials, hydroxyapatite (Ca10(PO4)6(OH)2, HAP) exhibited superior physicochemical and sorption properties, that is, low solubility in water, high specific surface area, high buffering capacity, and the high sorption capacities towards variety of cationic and anionic pollutants [93]. HAP is by far the most selective to U and Pb, due to the removal mechanism which involve dissolution of HAP and precipitation of thermodynamically more stable Pb and U containing phases [87, 94]. In soil, apatite matrices were highly effective for U uptake; however, the increase of organic matter content influenced the decrease of amendments efficiency [95]. Furthermore, the selectivity and capacity of HAP towards Pu, Co, Ni is very high, moderate for Sr, while low considering Cs and Tc [78, 81–84, 86–88].
\nComparing different apatite forms (synthetic, mineral, and biogenic), the product extracted from fish bones exhibited the best sorption properties, due to CO32− substitutions, low trace metal concentrations, poor crystallinity, and high microporosity necessary for optimal performance in the field [87]. Giving that this sorbent is produced from the commercial fish industry waste, it is both environmental friendly and cost-effective for large-scale operations. However, the bioavailability of essential trace elements was found to decrease at high HAP addition rates (5%), while uptake of As by plants was found to increase after HA treatment [96]. These results demonstrate that HAP application for the remediation of contaminated soil must be optimized and controlled.
\nIn addition to animal bones as the source material for apatite production, many other industrial by-products, wastes, and recycled materials are being tested as potential soil additives [65, 72]. In order to preserve natural mineral resources and reduce the costs of the immobilization treatments, application of such materials may represent a sustainable alternative. Another benefit comes from the reduction of the amount of accumulated wastes and their impact on the environment. Coal fly ash and bauxite residue (red mud) are mineral, oxide-based, residues, which exhibit high sorption potential for a range of radioactive pollutants [97–101].
\nFly ash has a silt loam texture (<90% of the particles having a diameter of <0.010 mm), and it is composed mainly of aluminosilicate structures, quartz, mullite, hematite, magnetite, and calcite [102]. The pH values of fly ash vary in the wide range 4.5–12.0, depending on the content of sulfur in the parent coal. Fly ash was considered as an additive in agriculture, for improving soil properties [102], and also as an additive for stabilization of heavy metals in polluted soil, with the promising results [103–105].
\nRed mud is by product obtained after bauxite processing, which primarily consists of Fe, Al, Si, and Ti oxides and zeolite-like minerals [106]. Due to the nature of Al extraction process, this material exhibits extremely high pH (10–12), and it is high capacity sorbent especially for pollutants in cation form. Numerous laboratory, pot, and field studies were conducted in the past years regarding red mud utilization in remediation of heavy metal polluted soils, and its potentials (both as a liming additive, and as a sorbent) have been demonstrated [107]. However, radionuclides, as pollutants, have gained much less attention and the further research in this field is encouraged.
\nIn general, there is a lack of the long-term studies on the overall effects of waste material additions on the soil properties. The variation in the composition of waste material and by-products adds uncertainty to their performance, and moreover, leaching of potentially hazardous substances from the waste material itself must be carefully evaluated. The activity levels of natural radinuclides can be elevated in fly ash and red mud with respect to parent coal and bauxite ore, therefore, a special attention should be paid to this aspect in order to keep activity levels in the permitted limits for soil.
\nThe source term and a wide variety of soil and environmental parameters affect the radionuclide behavior in terrestrial systems. Weaker bonds between the pollutant and soil components implicate higher mobility of pollutant, higher potential to get into the solution and to be adopted by the biota. In addition to total concentration of the pollutant, understanding of its environmental behavior by determining distribution pattern in different fractions of the soil is of principal importance for the selection of optimal remediation technologies. Due to the large number of factors that affect the outcome of the soil rehabilitation process, selection of optimal solution must be done on a case-by-case basis. Still, some guiding principles can be derived from the research studies and the practical experience: pollutants mainly bonded in exchangeable, carbonate and reducible phase are suitable for chemical extraction, while removal of contaminants from organic and residual fraction is neither economical nor feasible. Optimization of extracting solution composition, pH, the time, and the mode of the interaction with the soil are the perspective fields of research which must include the type of the soil and the radionuclide, and the effects of the extracting solution to other important soil characteristics. Analyzing the contamination level, the size and the properties of contaminated area,
This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Project III43009).
\nNowadays, the global increase in the number of people with chronic diseases as “cancer, diabetes, etc.” have affected the health and quality of life of many citizens around the world. For example, cancer is considered a public health problem because of its high incidence and mortality. The World Health Organization (WHO) estimates 27 million cases of cancer and 17 million deaths disease for the year 2030 [1]. Therefore, study on cancer treatment has attracted many scientists. Among therapies, cancer chemotherapy is widely used despite its disadvantages. Chemotherapy usually causes serious side effects because of the low selectivity of anti-cancer drugs, which affects not only cancer cells but also normal cells [2]. Thus, increasing attention is being paid to targeted drug delivery systems, which have been used to increase the efficiency of drug delivery to specific tissues and to decrease the associated side effects.
The most efficient solution is to use nanoparticles embedded in the hydrogel; this innovative-targeted drug delivery strategy involves coupling the drug to magnetic nanoparticles (NPs) that can be guided to the target using external magnetic fields [3]. Once they reach the target, the nanoparticles release the drugs under the influence of an alternating magnetic field [4]. Nanoparticle (NP) targeting has shown great potential for cancer drug delivery applications over the past decade. From nanoparticle targeting, magneto-particle have been widely studied because of their ability to target when an external magnetic field is applied [5].
An increasing population causes serious environmental pollution, waste production is also increasing and major proportion of by-products generated by contemporary food remains underused which may often contain precious substances. The crucial problem confronting by industries and society in food processing is the elimination of food waste. Chitin is an important natural resource and the world’s annual production of it is approximately 1010–1012 tons [6]. This latter is principally produced by mollusks, arthropods (crustaceans and insects) and fungi [7]. However, chitin and its derivatives have a high economic impact due to their numerous applications in the pharmaceutical [8], food [9, 10], cosmetics [11], textile [12], wastewater treatment and agricultural sectors [13].
In the past few decades, drug delivery systems (DDS) have been of great interest and resulted in many efforts to realize the effectiveness and targeted drug delivery tendency as well as to reduce the associated side effects [14]. However, DDS provide several advantages as compared to conventional dosages in terms of improved efficacy, reduced toxicity, improved patient compliance, and convenience [15]. Thus, the carriers used for drug release are generally biodegradable polymers which are extensively used for designing the control drug delivery systems [16].
On the other hand, with the rapid development of technology much attention has been given to use biopolymer based hydrogels in many applications including pharmaceuticals [17, 18], cosmetics [19], agriculture [20] and biotechnology [21, 22]. However, porous biomaterials fabricated from natural polymers “chitosan” were given significant attention for years. Chitosan is a unique natural cationic biopolymer produced by N-deacetylation of chitin and is the second most abundant natural polymer after cellulose [23]. Chitosan has been widely used in the biomedical field due to its superior properties including good biodegradability [24], biocompatibility [24], low toxicity [25, 26], mucoadhesive properties [27], antibacterial activity [28] and low cost [24, 29]. Chitosan is an excellent candidate for different applications particularly it has been employed in various FDA (Food and Drug Administration) approved biomedical applications. The -NH2 group of the (CS) chains is a pH-sensitive polymer with pKa around 6.5 due to variation of charge density at the pH range of 6–6.5, which is useful for wide range of pharmaceuticals applications. The pH value of the soluble-insoluble transition in the range 6–6.5 [30]. At pH levels beneath the pKa, high charge density of chitosan results in polyelectrolyte formation, in contrast at neutral pH, the low charge density of chitosan eases the intracellular release of biomolecules and contributes to its low cytotoxicity [31]. Chitosan has increasingly been used in the pharmaceutical field as it is one of the excellent choices for the Schiff’s base linkages to form an injectable hydrogel due to the nature of abundant amino groups on its backbone. Hydrogels from chitosan are usually prepared through physical interchain interaction or chemical reaction of the free amine groups with crosslinker agents (e.g. glutaraldehyde, glyoxal [32]). The disadvantage of these crosslinking agents, especially glutaraldehyde [33], benzaldehyde [34] and glyoxal is their toxicity to human tissues even at small traces [35], which has limited the use of chitosan hydrogels as scaffolds for drug delivery.
However, this paper discusses the recent trends in drug delivery systems (DDS) applications using macroscopic hydrogels. Hydrogel has received extensive attention due to its interconnected cross-linked porous hydrophilic polymer networks which can absorb large amounts of water or biological fluids. Additionally, hydrogels can be divided into three categories according to their size: macroscopic gels, nanogels (<200 nm), and microgels (0.5–10 μm). Hydrogels are promising, fashionable, intelligent and “smart” drug delivery vehicles that meet specific requirements for targeting drugs to specific sites and controlling drug release. The hydrogel-based drug carrier loaded with 5-fluorouracil (5-FU) drug for an up to 36 days sustained delivery has been studied by Xueyun Chen et al. [36].
Hydrogels are trendy, promising, intelligent and ‘smart’ drug delivery vehicles have become a great search field for targeting drugs to the specific sites and controlling drug release. Among several hardware platforms, ferrogels (FG) have a high potential for use in drug delivery. Ferrogels (FG) are consisting mainly of a polymer matrix embedded with magnetic micro and nano-particles (Fe3O4) [37, 38, 39]. Upon the application of an external magnetic field, the polymer matrix of the ferrogel can deform due to the magnetic force generated by the embedded magnetic particles, which would allow actuation and magnetically driven drug release on demand. The main advantage of ferrogels is that a larger quantity of drug can be loaded, compared to that transported by simple magnetic dispersion nanoparticles.
Ferrogel (FG) are typically prepared by incorporating magnetic particles into hydrogels [40]. Magnetic nanoparticles (Fe3O4) shown in Figure 1, have attracted much attention in the last few years as carriers for drug delivery systems. The potential use of nanoparticles as drug carriers has been presented in recent years as a major challenge, as nanoparticles have been designed to improve pharmacological and therapeutic effects in terms of reducing their toxic side effects. Besides, magnetite (Fe3O4) is considered as an important type of magnetic material with cubic inverse spinel structure. This property makes it very interesting because of its wide field of use, including magnetic recording, ferrofluid [41], catalyst [42] and some biomedical applications like magnetic resonance imaging (MRI) [43], bio separation [44], in addition to drug delivery system and therapeutic hyperthermia as well, to treat cancer and tumors [45]. Several methods have been developed recently for preparing magnetic nanoparticles, such as co-precipitation [46], sol–gel [47], solvothermal [48], sonochemical and chemical vapor deposition phase (CVD) [49]. Among these methods, co-precipitation is considered as the simplest, most efficient, and most economic method.
Model of crystal structure of magnetite (Fe3O4) and spherical Fe3O4 nanoparticles.
Ferrogels characterized by the presence of magnetic particles incorporated in polymer gels, are the subject of extensive research due to those magnetic particles and magnetic fields which have an extended application and clinical acceptance [50, 51]. Recent studies have shown controlled release of many drugs from ferrogels subject to magnetic fields [52, 53]. Ferrogels (FG) have made also injectable and biodegradable. However, typical drug delivery ferrogels have a disadvantage due to the cross-linking agent toxicity, which limits the macroporous biomaterials synthesis [37].
There are only a few reports in the literature on the synthesis of Fe3O4 by co-precipitation method. In this paper, a macroporous ferrogel which is sensitive to magnetic field was studied. Furthermore, we are probably the first scientific team that reports the preparation of novel hydrogels and ferrogels based on chitosan and oxidized chitosan as cross-linking agent embedded Fe3O4/drug (5-FU, caffeine and ascorbic acid). Figure 2 shows the magnetic drug delivery system under the influence of external magnetic field. The kinetics and in-vitro drug release profile of the drugs were studied in PBS pH (7.4) buffered solution at 37°C.
Schematic representation of magnetic drug delivery system under the influence of external magnetic field.
Chitosan (in powder form was prepared in our laboratory from exoskeletons of shrimp waste and purified, with degree of deacetylation >90% was determined by conductimetric titration), iron (II) sulfate heptahydrate (FeSO4.7H2O, sigma-Aldrich), iron (III) chloride (FeCl3.6H2O, Sigma-Aldrich), Caffeine (sigma-Aldrich), 5-Fluorouracil (sigma-Aldrich), Ascorbic acid (Fluka), Sodium metaperiodate (NaIO4, sigma-Aldrich), Hydrochloric acid (sigma-Aldrich), Ethylene glycol (sigma-Aldrich), Acetic acid (sigma-Aldrich), Sodium bicarbonate (Panreac), Sodium hydroxide (Sigma-Aldrich).
Oxidized chitosan (Figure 3) was prepared according to a previously reported method [54, 55]. The purified chitosan (1 g) ([GlcN] = 5.34 mM) was dispersed in 50 ml Hydrochloric acid solution HCl (10−3 M) at pH ranging from 4 to 5, and kept under magnetic stirring at 4°C for 30 min. Then 1 ml aqueous solution of sodium periodate 0.534 mM, P0 = 0.1 (P0 = moles of NaIO4 x moles of GlcN) was added to the mixture. The reaction system was covered with aluminum foil to prevent photo induced decomposition of periodate ion. The reaction lasted for 30 min at 4°C and it was interrupted by the addition of 1 ml ethylene glycol to inactivate any unreacted periodate in a molar ratio of 1:1. The oxidized derivative was washed by distilled water for 5 h and the dry product was obtained by freeze-drying.
Schematic representation of reaction between chitosan (CS) by sodium periodate.
The procedure for preparation of the hydrogel was as follows: chitosan (0.1 g) was dispersed in 10 ml of (1% acetic acid) at pH = 4.8 in an ice bath under magnetic stirring until a clear solution was obtained. Afterwards, the drug (5-FU 10 mg, Caffeine 10 mg or Ascorbic acid 10 mg) was added into the solution and gently stirred until the complete dissolution for 30 min. The oxidized chitosan (60 mg) was added to the solution of chitosan soluble drug under continuous stirring to facilitate crosslinking between amino of chitosan (NH2) and aldehyde groups of chitosan (OCS). Then the 6% (w/v) NaHCO3 solution was slowly added to the solution in an ice bath under magnetic stirring to get homogeneous mixture at pH = 7 [56], and a transparent gel was obtained as shown in Figure 4. The hydrogel was washed with ethanol, and filtered to remove traces of unreacted reagents.
Schematic representation of the chemical (CS)/(OCS) cross-linking mechanism and the formation of the hydrogel.
According to the previous work, magnetite (Fe3O4) nanoparticles were synthesized by chemical co-precipitation method. Magnetic Fe3O4 NPs were synthesized by dissolving 50 mL of FeCl3.6H2O and 25 mL of FeSO4.7H2O in 350 mL of distilled water under nitrogen atmosphere under vigorous stirring. Upon addition of (35 ml) NaOH, the pH was adjusted to about 10, the solution turned black, indicating the formation of magnetite nanoparticles. Further stirring is continued for 1 h to uniformly disperse the magnetic nanoparticles. After raising the reaction temperature to 80°C. Then, a formed black precipitate was collected with an external magnet, washed several times with ethanol and distilled water, and dried in vacuum at 60°C. The entire reaction is given by the equation as shown in Figure 5.
Representation of superparamagnetic magnetite nanoparticles synthesis technique.
Firstly, chitosan solution was prepared by dissolving 0.1 g chitosan (CS) in 10 mL acetic acid solution (1%). 50 mg iron oxide nanoparticles were mixed with chitosan solution and stirred for 2 h at 40°C to give chitosan coated magnetic nanoparticles (CS-Fe3O4). Then, the drug (5-FU 10 mg, Caffeine 10 mg or Ascorbic acid 10 mg) was added into the solution (CS-Fe3O4) and gently stirred for 30 min. 60 mg of oxidized chitosan (OCS) was added as crosslinking agent and were mixed with (CS-Fe3O4) solution. The reaction mixture was stirred at 0°C for 3 hours. The pH of the solution was adjusted to pH = 7 with 6% (w/v) NaHCO3. The product (CS-Fe3O4-OCS) was washed with deionized water. Figure 6 shows a representation of the prepared drug delivery ferrogel.
Representation of superparamagnetic drug delivery hydrogel.
Fourier transform infrared (FTIR) spectra of the chitosan, oxidized chitosan, CS/OCS hydrogel, CS/drug/OCS lyophilized hydrogel, Fe3O4 NPs and the freeze-dried CS/Fe3O4/OCS ferrogel were obtained from discs containing 2.0 mg dry sample in approximately 198 mg potassium bromide (KBr). The measurements were recorded by a Perkin–Elmer FTIR spectrophotometer at the resolution of 4 cm−1 in the wave number region 400–4000 cm−1.
The thermal properties of lyophilized hydrogel, pure chitosan, oxidized chitosan, Fe3O4 NPs and CS/Fe3O4/OCS lyophilized ferrogel were investigated by thermogravimetric analysis (TGA). Samples were placed in the balance system and heated from 40 to 800°C at a heating rate of 10°C/min using a TA Instruments TGA (Q500) device.
The saturation magnetization of Fe3O4 NPs, CS-Fe3O4-OCS ferrogel was measured by vibrating sample magnetometer VSM (SQUID model MPMS XL 7) from Quantum at room temperature between magnetic fields of −14,000 (Oe) to 14,000 (Oe).
The chitosan-based hydrogels cross-linked with oxidized chitosan was frozen at −75°C for 24 h and then lyophilized (by Alpha 1–2 LDplus) for 48 h. The lyophilized sample was obtained and then examined by a scanning electron microscopy (SEM) (Mini SEM Hirox SH-4000).
Freeze-dried CS/OCS hydrogel were immersed in phosphate-buffered saline (PBS) at 37°C (pH = 1.2, pH = 5.8 and pH = 7.4). The samples were weighed before being put into PBS (W0). After the vial was sealed and held at 37°C for 24 h, and the excess solution on the surface of the hydrogels was quickly absorbed with filter paper [55]. The equilibrium-swelling ratio (SR) was calculated using the following equation:
where, Wd is the weight of dry hydrogel after lyophilization and Ws is the weight of swollen hydrogel.
(5-FU, caffeine or ascorbic acid) was selected and used as a model drug in the release experiments. In vitro drug release test was performed in a phosphate buffer solution PBS (pH 7.4 at 37°C) under shaking. The hydrogels and ferrogels (m = 1.14 g) (3 cm x 4 cm) were placed in a cartouche before immersing in 1000 mL of phosphate-buffered saline (PBS). At predetermined time intervals, 5 mL of release medium was withdrawn. Then 5 mL of fresh buffer was added to the original to maintain the total volume. The drug release was determined by UV–Vis spectrophotometry at λmax (5-Fluorouracil (266 nm), caffeine (273 nm) and ascorbic acid (265 nm)). The concentration of the active ingredient in the (PBS, pH = 7.4 at 37°C) has been achieved from the calibration curve, and the amount of drug released at time t (Mt) was calculated by accumulating the total active ingredient release up to that time. In vitro drug release tests were performed in triplicate (n = 3). There are a few steps, which mainly control drug release phenomena from the polymer matrix, dissolution of the drug, liquid penetration into the matrix and diffusion of the drug from the drug encapsulated in the matrix. In order to understand the release kinetics and the mechanism of the active ingredient release, release kinetics data obtained in vitro using ferrogels and hydrogels are fitted with kinetics model. The release data are best fitted with the Korsmeyer−Peppas (KP) model. The (KP) model deal with Eq [57]:
where “Mt” is the amount of drug released at time (t), “M0” is the maximal amount of the drug released at maximum interval. It is interesting to note that three drugs (5-FU, caffeine and ascorbic acid) in hydrogels exhibit a Fickian nature of drug diffusion. However, the interaction of the drug molecules with the matrix play an important role in the drug release kinetics occurring through a diffusion mechanism.
The experimental data are expressed as the mean values of at least three replicates ± standard deviation (SD). The results were analyzed and showed usage Kaleida graph.
The concept of this study is depicted in (Figure 7). Oxidized chitosan (OCS) was prepared following a well-known method where chitosan is oxidized with sodium periodate (NaIO4). Oxidization of chitosan created multiple aldehyde groups all along the polymeric chain using the method described in literature [54, 58]. The hydrogels and ferrogels (magnetic Fe3O4 embedded in novel hydrogel) were prepared by crosslinking chitosan (CS) with oxidized chitosan (OCS). The crosslinking of hydrogel and ferrogel was achieved by (–C=N-) bonds of Schiff-base reaction. Our results indicate that the process synthesis of the hydrogel and ferrogel was embedded with three drugs (5-FU, caffeine and ascorbic acid) has successfully loaded in the carrier polymeric. The schematic representation of smart ferrogel “magnetic hydrogel” was shown in (Figure 7).
Schematic representation of (CS-Fe3O4-OCS) ferrogel.
The Figure 8 shows the procedure for preparation of the hydrogel and a photograph of (CS-drug-OCS) hydrogel.
Schematic representation of the synthesis process of CS/drug/OCS hydrogel.
The IR spectrum of CS, OCS, (CS/OCS) and (CS/drug/OCS) lyophilized hydrogel are listed in (Figures 9 and 10) and major functional moieties are labeled with wavenumbers was recorded in the region of 4000–40 cm−1. The FTIR spectrum of pure chitosan (Figure 9(a)) shows wide band around 3450 cm−1 corresponding to amine N–H symmetrical vibration and H bonded O–H group. The peak observed between 3400 and 3700 cm−1 corresponding to combination of the band O-H, NH2 intra and intermolecular hydrogen bonding. The peaks at 2920 and 2320 cm−1 are assigned to the symmetric and asymmetric may be attributed to –CH vibrations of carbohydrate ring [59]. The bands at 1650 cm−1 and 1545 cm−1 may be attributed to C=O stretching (amide I vibration) and N-H bending (–NH2 bending of amide II) in amide group, respectively and 1390 cm−1 (N–H stretching or C–N bond stretching vibrations, amide III vibration) [60]. The peak observed at 1050 cm−1 has the contribution to the symmetric stretching of C–O–C groups. The absorption peaks in the range 900–1200 cm−1 are due to the antisymmetric C–O stretching of saccharide structure of chitosan. In order to understand the oxidation of oxidized chitosan (OCS), the FTIR spectra results for (OCS) in (Figure 9(b)) verified successful oxidation, while a new absorption peak appeared around 1725 cm−1 [55], which was assigned to an aldehyde group (-C=O) bond, indicating that the CS has been successfully oxidized by the NaIO4 [61]. Furthermore, the peak (Figure 9(c) at 1637 cm−1 caused by C=O and C=N is reduced significantly. These differences indicate that the aldehyde groups of OCS reacted with the amino groups of CS to generate a Schiff base”imine” [62]. FTIR analysis was performed (Figure 9(d)) exhibits the IR spectra of the prepared nanoparticles. The spectrum of Fe3O4 magnetic nanoparticles shows the formation of two strong absorption bands between 636 cm−1 and 592 cm−1. Furthermore, the band at 592 cm−1 was confirmed as the Fe-O stretching vibration of tetrahedral sites of spinel structure. The absorption bands at 459 cm−1, assigned to tetrahedral and octahedral sites, peaks at 3400 cm−1 due to the O-H stretching model adsorbed on the surface of the Fe3O4 nanoparticles [63].
FTIR spectra of (a) chitosan, (b) oxidized chitosan, (c) CS/OCS lyophilized hydrogel, (d) Fe3O4 NP.
FTIR spectra of (a) CS/a.AS/OCS lyophilized hydrogel, (b) CS/CAF/OCS lyophilized hydrogel; (c) CS/5FU/OCS lyophilized hydrogel.
For the spectra of three drugs (5-FU, caffeine and ascorbic acid) loaded (CS/OCS) in hydrogels (Figure 10); exhibited the characteristic absorption of imine stretching vibration (-C=N–) at 1637 cm−1 [54, 64], suggests that the coupling reaction was occurred between –CHO of OCS and –NH2 of CS.
The measurements of the magnetic field-dependence of the magnetization of the uncoated and coated magnetite nanoparticles at 25°C are presented in (Figure 11). The plots indicate that both samples exhibit superparamagnetic behavior with zero remanence and coercivity. (Figure 11) shows the magnetic curves as a function of applied field at room temperature obtained for Fe3O4 and CS-Fe3O4-OCS ferrogel, respectively. The magnetization saturations were found to be 60.57 emu/g for Fe3O4, 17.25 emu/g for CS-Fe3O4-OCS ferrogel [65]. The magnetization value decreased after coating due to the existence of oxidized chitosan and chitosan, which formed polymerized multilayers. It can be concluded that the Ms. value of CS/Fe3O4/OCS ferrogel is less than the Fe3O4 (NPs) that can be attributed to the creation of a non-magnetic polymer layer around Fe3O4 (NPs) in the hydrogel [66]. Taking into account the magnetic properties of the prepared by ferrogel, it may be able to deliver the drug to the target area in the presence of an external magnetic field.
The magnetic hysteresis loops for Fe3O4 NPs and CS@Fe3O4@OCS hydrogel measured by SQUID at room temperature.
A perfect injectable hydrogel must have pores in the range of 50–100 μm and a high degree of interconnectivity to facilitate nutrient and oxygen transport, as well as cell adhesion and migration. By using SEM, we studied the pore size distribution in hydrogels (Figure 12). In this study, morphology of freeze-dried hydrogel (CS/OCS) were observed with scanning electron microscope (SEM). As can be seen in (Figure 12), the (CS/OCS) lyophilized hydrogel had continuous and porous structures with interconnecting pores, pores diameter ranging from several tens to several thousands of micrometers [55]. Moreover, the more crosslinking between amino group and aldehyde group, the diameter of the pores are decreased and the compactness of pores increased. The micrographs of CS/OCS hydrogel it was clearly observed that the hydrogel had a three-dimensional porous structure, which was beneficial for drug delivery systems.
Micrographs of chitosan cross-linked oxidized chitosan hydrogel at low and high magnification.
To evaluate the thermal stability of the chitosan (CS) oxidized chitosan (OCS) and (CS/OCS) lyophilized hydrogel, TGA thermograms were obtained as shown in (Figure 13). The TGA of pure chitosan shows two-stage weight loss in the range 40 to 750°C (Figure 13), it is clear that chitosan started to degrade at 40–130°C with 8% weight is due to the loss of water molecules. Initial decomposition around 130°C for pure chitosan can be attributed to the strong water adsorptive nature of chitosan. The second stage of degradation occurred at 340°C and continued up to 460°C [67]. There was 38.43% weight loss occurring in the second stage due to degradation of pure chitosan biopolymer and the temperature at which maximum degradation observed was 274.74°C. At the end of 750°C, the total weight loss of sample was 100% [54, 67]. TGA of oxidized chitosan (OCS) showed two steps of degradation (Figure 13), the first stage ranges between 40 and 130°C and shows about 8.2% loss in weight corresponded to water release for the initial step. The second stage decomposition was observed from 300°C and continued up to 460°C, during this time there was 39% weight loss due to the degradation of chitosan. At the end of 700°C, the total weight loss of sample was 90% [10, 54]. For CS/OCS lyophilized hydrogel, the degradation starts at a lower temperature compared to chitosan and oxidized chitosan (Figure 13). For the CS/OCS hydrogel, shows two-stage weight loss in three stages. The first stages of degradation takes place from 40 to 160°C with a weight loss of 13% could be due to the loss of both the loosely bound water and tightly bound water [68]. The free water and hydrogen-bonded water are released at a temperature between 40 and 100°C. The hydrogel contains many hydrophilic groups that retain water more tightly in the hydrogel skeleton by polar interaction. As a result, it is harder to lose. Thus, this tightly bound water is released in the temperature region 100–156°C. The second stage of hydrogel degradation started between 160° C and 385° C with a 41% weight loss. The three-stages of degradation biopolymers, at the end of 700°C, the total weight loss of sample was 90%. This phase of the weight loss mainly could be caused by a series of thermal and oxidative decomposition in the process including dehydration of the sugar cycle, degradation, N-deacetylation of the molecular chain of the chitosan cracking unit and vaporization and removal of volatile products. It can be concluded the TGA curve shows at about 222°C. This is probably due to the formation of (-C=N-) and this proves that biopolymer-based Schiff base is thermally less stable.
TGA graphs of chitosan (CS), oxidized chitosan (OCS) and (CS/OCS) lyophilized hydrogel.
The TGA curves of uncoated Fe3O4 and the lyophilized ferrogel (CS-Fe3O4-OCS) are shown in Figure 14. For uncoated Fe3O4 NPs (Figure 14(a)), the TGA curve showed that the weight loss over the temperature range 40–750°C was about 2.2%. Hence, this weight loss is related to removal of the physically adsorbed water and/or hydroxyl groups on the surface of Fe3O4 nanoparticles. For coated nanoparticles Fe3O4. Similarly, the weight curve of CS/Fe3O4/OCS (Figure 14(b)) showed a progressive decrease of 85%. This is due to the degradation of the polymer and hydrogen-bound water in the temperature range of 40–166°C, which forms the polysaccharide structure of OCS and CS. In addition, a uniform and steady decrease in weight loss at 166–630°C is CS/Fe3O4/OCS was observed. This may be partly attributed to the degradation and decomposition of organic skeletal structure, amino groups, and other functional groups. By comparing the curves of CS/Fe3O4/OCS and Fe3O4, it was observed that Fe3O4 particles are wrapped into CS and OCS can enhance the thermal stability of the whole system. A temperature of 630°C or higher, the remaining material was carbonized completely. The indicated that chitosan and oxidized chitosan coated Fe3O4 successfully and penetrated deeply into in the matrix CS/OCS.
TGA curves for a) uncoated Fe3O4 b) CS-Fe3O4-OCS lyophilized ferrogel.
To investigate the pH dependent swelling behavior of the CS/OCS hydrogels for drug delivery, PBS with (pH = 1.2; pH = 5.8 and pH = 7.4) at T = 37°C were used to simulate the physiological medium and were used for testing swelling of the hydrogels. The results of the equilibrium-swelling ratio are presented in (Figure 15). The CS/OCS hydrogels showed large differences in swelling behavior at different pH values. The pKa value of the D-glucosamine residue in chitosan was approximately 6.2 to 7.0. Therefore, the amino groups in the chitosan were protonated and positively charged in acidic PBS (pH = 1.2 and pH = 5.8), and the electrostatic repulsion between positively charged -NH3+ groups would lead to swelling of the hydrogels. The % equilibrium swelling values were found to be higher at pH = 1.2, than at pH = 7.4. This can be explained by protonation of the unreacted NH2 groups of chitosan at acidic pH, leading to dissociation of the hydrogen bonding involving the amino groups, and thus facilitating the entry of the solvent into the material. The swelling process of hydrogels involves the ionization [69]. Furthermore, the Schiff base bonds between -NH2 and -CHO as a cross-linker became weak in PBS (pH = 7.4 at 37°C); the swelling ratio of CS/OCS was 350%, resulting in swelling of the hydrogel. Therefore, the CS/OCS hydrogel in PBS (pH = 1.2 at 37°C) exhibited the largest swelling ratio of 670%; the swelling ratio (pH = 5.8 at 37°C) was 509%. The decreased swelling ratio occurred due to increased crosslinking density in the hydrogels. Meanwhile, the equilibrium swelling ratios of the hydrogels in a pH = 7.4 solution dramatically decreased. This is because hydrogels exhibited pH-responsive swelling behavior, and the hydrogels showed a much higher swelling ratio in an acidic medium than that in a pH 7.4 medium.
% Swelling of CS/OCS hydrogel in buffer solutions of pH = 1,2, pH = 5,8 and pH = 7,4 at T = 37°C.
The model drugs (5-FU, caffeine and ascorbic acid) was encapsulated in the hydrogel matrix used for the release kinetics in PBS (pH = 7.4 at 37°C) are depicted in (Figure 16). The purpose here was to study whether the release of the drug trapped in the hydrogels, as well as by the simple diffusion. In a system, where drug is entrapped in a biodegradable matrix, the release rate depends on three parameters: the size of the drug molecule, the drug solubility (soluble-sparingly soluble-insoluble), the cross-linking density and the degradation rate. The ability of the chitosan-imine-oxidized chitosan hydrogels to act as matrix for controlled release was investigated in vitro by monitoring the release profile of the (5-FU, caffeine and ascorbic acid) three-model drug from system in phosphate buffer of physiological pH (7.4), at the human body temperature of 37°C (Figure 16). In order to study the release behavior of 5-FU, caffeine, ascorbic acid incorporated in the chitosan-based hydrogel cross-linked by oxidized chitosan, they were incubated in release media (phosphate buffer pH = 7.4 at 37°C) and evaluated by UV spectrophotometry. (Figure 16) shows release profiles of 5-FU, caffeine and ascorbic acid up to 26 h of incubation period. As shown in (Figure 16), the chitosan hydrogels showed an initial burst release of 5-FU, caffeine and ascorbic acid over a period of 3 h for all incubation media, which was of the order of (5 -FU “52%”, caffeine “43%” and ascorbic acid “60%”). This initial rapid release, characterized by a “burst effect», because certain quantities of 5-FU, caffeine and ascorbic acid were localized on the surface of the hydrogels by adsorption which could be released easily by diffusion. After 3h the release percentages of (5-FU “86%”, caffeine “89%” and ascorbic acid “91%”), respectively [70]. The remaining part of the drug can be trapped in hydrogels because the amino functions of chitosan can enter into the Schiff reaction with the aldehyde groups of oxidized chitosan. Indeed, the hydrogel contained large pore size, which is beneficial for the diffusion of the drug, this initial bursting effect, a slower sustained and controlled release occurred throughout the incubation period and the amount of release. The release profiles confirmed that the (5-FU, caffeine and ascorbic acid) drugs were encapsulated in hydrogels.
In vitro release of 5-FU, caffeine and ascorbic acid embedded in hydrogels (pH = 7,4 at 37°C). Values reported are an average of n = 3 ± standard deviation.
As shown in Figure 17, magneto-hydrogel showed an initial burst release of (5-FU, caffeine and ascorbic acid) in a period of 5 h, which was in the range of (37%, 34%, and 42%). The initial burst phase is caused by drug adsorbed on the surface of the nanoparticles Fe3O4 embedded in hydrogel. The release kinetics at pH = 7.4 at 37°C within 45 h clearly indicated that Fe3O4 embedded in hydrogel influenced drugs release. At pH = 7.4 at 37°C, about (95%, 93% and 97%) amounts of 5-FU, caffeine and ascorbic acid were release after 45 h, respectively. Due to the slower swelling rate of nanotransporters in solution, the rate of drug release is also slower. It is well known that there are a large number of amino and hydroxyl groups on the surface of chitosan molecules, which provide functional groups and favorable characteristics for biological molecules. In PBS (pH = 7.4 at 37°C), amino groups of chitosan mainly attach to the surface of the nanoparticles, so as to reduce the surface voids and render the pore blockage, lower penetration, and thus slow down the release rate of the drug [36]. However, due to the magnetic orientation role of MNPs, magnetic nano-drug carriers could be transported by applying an external magnetic field and maintain drug concentration for extended periods. Such rapid transport and slow release of the nanocarriers to the target site may be desirable for many biomedical applications, minimizing drug leakage to undesirable sites and reducing the risk of heart attack due to high dose in a short period of time. These results clearly illustrated that the chitosan hydrogel containing Fe3O4 resulted in a barrier system for the sustained release of 5-Fu, caffeine and ascorbic acid. We speculate that this barrier structure would block the drug loss in the early burst release, which is benefit to reduce the toxic side effects.
Cumulative release profiles of 5-FU-gel, caffeine-gel, ascorbic acid-gel with external magnetic field. Values reported are an average of n = 3 ± standard deviation.
Many conclusions can be made from the present work, the ferrogels (FG) are cross-linked polymer networks containing magnetic nanoparticles: a) magnetic magnetite (Fe3O4) were synthesized successfully by chemical co-precipitation and has been confirmed using FT-IR, VSM analysis, TGA. The advantage of the co-precipitation method are low cost, rapidity, ease, reproducibility and high-yield synthesis. b) The hydrogel was formulated by cross-linking chitosan (CS) and oxidized chitosan (OCS) via the Schiff-base (-C=N-) reaction. Obviously, these results indicate that this exhibit non-toxic, biodegradable, good injectability, less expensive and respect the environment, quick gelation time, in vitro pH-dependent equilibrated swelling ratios, interconnected porosity. c) Magneto-responsive hydrogels are typically prepared by incorporating magnetic particles into hydrogels and has been confirmed using (FT-IR), (TGA), (VSM) analysis at room temperature. d) The role of Fe3O4 embedded in hydrogel, which allows reducing the surface voids and rendering the pore blockage, lower penetration, and thus slowing down the release rate of the drug. e) A 5-Fluorouracil (5-FU), caffeine and ascorbic acid release tests were used to demonstrate the excellent in vitro drug release behavior of these hydrogels and ferrogels. However, all these results indicate that this type of biomaterial based on chitosan with oxidized chitosan in the presence of the three drugs with different solubility for the preparation of hydrogels effective for the controlled release of the drug. Compared to other hydrogels based on chitosan, the present study brings to the attention of researchers a novel strategy to design a non-toxic and biodegradable matrix for drug delivery systems, by the simple use of appropriate oxidized chitosan without incorporating any crosslinking agents. This design expands the variety of hydrogel matrices, guiding additional efforts in the development of the new ideas for pharmaceuticals applications. As a perspective and future challenges, we will test this type of ferrogels for cancer treatment by hyperthermia.
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',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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In particular, the main classes of soil pollutants in Europe (heavy metals, mineral oils, polycyclic aromatic hydrocarbons (PAHs), monoaromatic hydrocarbons, phenols and chlorinated hydrocarbons (CHCs)), together with the emerging contaminants (i.e. endocrine-disrupting chemicals (EDCs) and pharmaceutical-personal care products (PPCPs)) are considered. A description of the fungal species (saprotrophic and biotrophic basidiomycetes) and biodegradative extracellular (laccases and class II peroxidases) and intracellular (cytochrome P450 monooxygenases and glutathione transferases) enzyme classes is reported. Moreover, the chemical-physical parameters that influence the biodegradation process are examined, and the biostimulation and bioaugmentation strategies are described. A specific attention is paid to the microcosm studies, at the laboratory scale, which are an essential approach to evaluate the feasibility of a biodegradation process.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Francesca Bosco and Chiara Mollea",authors:[{id:"93865",title:"Dr.",name:"Francesca",middleName:null,surname:"Bosco",slug:"francesca-bosco",fullName:"Francesca Bosco"},{id:"96159",title:"Dr.",name:"Chiara",middleName:null,surname:"Mollea",slug:"chiara-mollea",fullName:"Chiara Mollea"}]},{id:"68347",doi:"10.5772/intechopen.88339",title:"Bioremediation of Heavy Metals",slug:"bioremediation-of-heavy-metals",totalDownloads:1504,totalCrossrefCites:4,totalDimensionsCites:9,abstract:"Exposure to lead (Pb), zinc (Zn), cadmium (Cd), copper (Cu), and selenite (SeO3−2) consider the main heavy metals that threat human health. These heavy metals can interfere with the function of vital cellular components. Soil heavy metal contamination represents risks to humans and the ecosystem through drinking of contaminated groundwater, direct ingestion or the food chain, and reduction in food quality. Bioremediation means cleanup of polluted environment via transformation of toxic heavy metals into less toxic form by microbes or its enzymes. Otherwise, bioremediation by microbes has limitations like production of toxic metabolites. The efflux of metal ions outside the cell, biosorption to the cell walls and entrapment in extracellular capsules, precipitation, and reduction of the heavy metal ions to a less toxic state are mechanisms to metals’ resistance.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Medhat Rehan and Abdullah S. Alsohim",authors:[{id:"175766",title:"Dr.",name:"Medhat",middleName:null,surname:"Rehan",slug:"medhat-rehan",fullName:"Medhat Rehan"}]},{id:"68268",doi:"10.5772/intechopen.88207",title:"Arsenic Phytoremediation: Finally a Feasible Approach in the Near Future",slug:"arsenic-phytoremediation-finally-a-feasible-approach-in-the-near-future",totalDownloads:1094,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Arsenic, a class-1 carcinogenic, is a ubiquitous metalloid found in the atmosphere, soils, natural waters, and organisms. The World Health Organization (WHO) estimates that hundred million people worldwide might be chronically exposed to arsenic in drinking water at concentrations above the safety standard. Conventionally applied techniques to remove arsenic species show low removal efficiency, high operational costs, and high-energy requirements. The biological methods, especially phytoremediation, could be cost-effective for protecting human health and the environment from toxic metal contamination. Plants, as sessile organisms, have developed an extraordinary capacity to tolerate arsenic through three main strategies: uptake repression, sequestration into the vacuole, or extrusion. Therefore, arsenic perception and tolerance require a coordinated response that involves arsenic transporters, extrusion pumps, vacuole transporters, and the activation of the phytochelatin biosynthetic pathway. For phytoremediation to become a feasible strategy for arsenic removal from contaminated sites, it is essential to completely understand the molecular mechanisms of arsenic uptake, extrusion, and sequestration, as well as how this response is coordinated. The new genome-wide technologies provide a unique opportunity to understand the molecular mechanisms underlying arsenic perception and accumulation in plants that will open up new possibilities for phytoremediation of arsenic-contaminated waters and soils.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Cristian Mateo, Micaela Navarro, Cristina Navarro and Antonio Leyva",authors:null},{id:"69539",doi:"10.5772/intechopen.84208",title:"Greenhouse Gas Emissions of Agriculture: A Comparative Analysis",slug:"greenhouse-gas-emissions-of-agriculture-a-comparative-analysis",totalDownloads:734,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Greenhouse gas emissions are accounted by greenhouse gases inventories, which must be produced by common accounting rules, called Guidelines, which are endorsed by the United Nations Framework Convention on Climate Change (UNFCCC). These inventories are fundamental to analyze the impact of agriculture on emissions, and as example of the difficulty and complexity of implementation of the guidelines, a comparative study is made on emissions from Agricultural Soil Management (CRF category 3D source) utilizing biological nitrogen fixation. The analysis carried out for the N2O emissions under this section of the agrarian sector of Spain, Europe, New Zealand, Canada and the USA, inventories and national communications from Argentina and Brazil permit to observe the wide spectrum of approaches and the importance of the management of the accounting rules to be used mainly if we need that the impact of mitigation policies are captured in a direct way by the inventory. New technologies could introduce changes in the rules and can be utilized for reducing emissions, and examples are also analyzed.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Dionisio Rodríguez",authors:null},{id:"65795",doi:"10.5772/intechopen.84548",title:"Progressive Research in the Molecular Mechanisms of Chronic Fluorosis",slug:"progressive-research-in-the-molecular-mechanisms-of-chronic-fluorosis",totalDownloads:1124,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Long-term excessive intake of fluoride (F) leads to chronic fluorosis, resulting in dental fluorosis and skeletal fluorosis. Chronic exposure to high doses of fluoride can also cause damage to soft tissues, especially when it passes through the blood-brain, blood-testis, and blood-placenta barrier, causing damage to the corresponding tissues. Fluorosis has become a public health problem in some countries or regions around the world. Understanding the pathogenesis of fluorosis is very important. Although the exact mechanism of fluorosis has not been fully elucidated, various mechanisms of fluoride-induced toxicity have been proposed. In this chapter, we will introduce the research progress of the mechanism of fluorosis, focusing on dental fluorosis, skeletal fluorosis, nervous and reproductive system toxicity, and influential factors related to fluoride toxicity (i.e., genetic background, co-exposure with other element). In addition, the application of proteomics and metabolomics in the study of the pathogenesis of fluorosis is also introduced. Currently, there is still no specific treatment for fluorosis. However, since fluorosis is caused by excessive intake of fluoride, avoiding excessive fluoride intake is the critical measure to prevent the disease. In endemic regions, health education and supplement diet with vitamins C, D and E, and calcium and antioxidant compounds are important.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Liming Shen, Chengyun Feng, Sijian Xia, Yan Wei, Hua Zhang, Danqing Zhao, Fang Yao, Xukun Liu, Yuxi Zhao and Huajie Zhang",authors:null}],mostDownloadedChaptersLast30Days:[{id:"68347",title:"Bioremediation of Heavy Metals",slug:"bioremediation-of-heavy-metals",totalDownloads:1504,totalCrossrefCites:4,totalDimensionsCites:9,abstract:"Exposure to lead (Pb), zinc (Zn), cadmium (Cd), copper (Cu), and selenite (SeO3−2) consider the main heavy metals that threat human health. These heavy metals can interfere with the function of vital cellular components. Soil heavy metal contamination represents risks to humans and the ecosystem through drinking of contaminated groundwater, direct ingestion or the food chain, and reduction in food quality. Bioremediation means cleanup of polluted environment via transformation of toxic heavy metals into less toxic form by microbes or its enzymes. Otherwise, bioremediation by microbes has limitations like production of toxic metabolites. The efflux of metal ions outside the cell, biosorption to the cell walls and entrapment in extracellular capsules, precipitation, and reduction of the heavy metal ions to a less toxic state are mechanisms to metals’ resistance.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Medhat Rehan and Abdullah S. Alsohim",authors:[{id:"175766",title:"Dr.",name:"Medhat",middleName:null,surname:"Rehan",slug:"medhat-rehan",fullName:"Medhat Rehan"}]},{id:"68504",title:"Biological Remediation of Phenoxy Herbicide-Contaminated Environments",slug:"biological-remediation-of-phenoxy-herbicide-contaminated-environments",totalDownloads:1005,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Phenoxy herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) are widely used in agriculture to control broadleaf weeds. Although their application has helped to increase the yield and value of crops, they are also recognized as a source of emerging environmental contamination. Their extensive use may promote contamination of soil, surface, and groundwater and lead to increased inhibition of plant development and soil toxicity. Hence, there is an urgent need to identify nature-based methods based on appropriate biological remediation techniques, such as bio-, phyto-, and rhizoremediation, that enable the effective elimination of phenoxy herbicides from the environment. Bioremediation typically harnesses microorganisms and their ability to utilize recalcitrant contaminants in complete degradation processes, while phytoremediation is a cost-effective, environmentally friendly strategy that uses plants to transform or mineralize xenobiotics to less or nontoxic compounds. Rhizoremediation (microbe-assisted phytoremediation), in turn, is based on the interactions between plant roots, root exudates enriched in plant secondary metabolites, soil, and microorganisms. Based on the above, this chapter presents current knowledge on the properties of phenoxy herbicides, as well as the concentrations detected in the environment, their toxicity, and the biological remediation techniques used for safe removal of the compounds of interest from the environment.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Magdalena Urbaniak and Elżbieta Mierzejewska",authors:null},{id:"70249",title:"Bioremediation of Petroleum-Contaminated Soil",slug:"bioremediation-of-petroleum-contaminated-soil",totalDownloads:1132,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Petroleum is not only an important energy resource to boost the economic development, but also a major pollutant of the soil. The toxicity of petroleum can cause a negative impact on ecosystem, as well as the negative effects related to its carcinogenic for both animals and humans. In the present study, bioremediation as an alternative tool for restoration petroleum-contaminated soils was set forth, and focusing on the phytoremediatior plants, petroleum-biodegradable microorganism are responsible for the biodegradation of petroleum. In the present chapter, the bioremediation of petroleum-contaminated soil, as well as the influence factors of bioremediation are elaborated based on the recently studies. This will provide a novel understanding on bioremediation and help improve strategies for petroleum-contaminated soils remediation.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Shuisen Chen and Ming Zhong",authors:null},{id:"63252",title:"Adsorptive Removal of Fluoride onto Different Waste Materials: Orange Juice Residue, Waste Seaweed, and Spent Cation-Exchange Resin",slug:"adsorptive-removal-of-fluoride-onto-different-waste-materials-orange-juice-residue-waste-seaweed-and",totalDownloads:1083,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"To effectively use waste materials in developing a sustainable society, adsorbents for removing trace or low concentrations of fluoride, which is difficult to be removed by conventional techniques, were prepared from three waste materials: orange juice residue, waste sea weed, and spent cation exchange resin. These adsorbents were loaded with tri- or tetravalent metal ions such as iron(III) and zirconium(IV), of which zirconium(IV) was found to be most suitable as the loaded metal ion. From the pH effect on adsorption, the adsorption mechanism was inferred, and adsorption and desorption was found to be controlled by changing pH values. The maximum adsorption capacities on zirconium(IV)-loaded orange juice residue, waste sea weed, and spent cation exchange resin were evaluated as 33.1, 18.1, and 37.6 mg/g, respectively, which were higher than those of most other adsorbents reported in literatures. They exhibited high selectivity for fluoride over other anionic species and high durability. Tests to remove trace concentrations of fluoride from actual waste plating solutions revealed that the concentration could be reduced below the acceptable level using small amounts of these adsorbents, i.e., it was reduced lower than 1.5 mg/dm3 (WHO standard) by adding 1 g of the adsorbents into 1 dm3 test solution.",book:{id:"8796",slug:"environmental-chemistry-and-recent-pollution-control-approaches",title:"Environmental Chemistry and Recent Pollution Control Approaches",fullTitle:"Environmental Chemistry and Recent Pollution Control Approaches"},signatures:"Katsutoshi Inoue, Hari Paudyal, Hidetaka Kawakita and Keisuke Ohto",authors:null},{id:"63393",title:"Characterization of the Youssoufia-Morocco-MineFluoride-Contaminated Water and Their Detrimental Effects on Human Health",slug:"characterization-of-the-youssoufia-morocco-minefluoride-contaminated-water-and-their-detrimental-eff",totalDownloads:851,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"In Youssoufia, the second phosphate mining center of our country (Morocco), the drinking water needs of the rural population are of underground origins. Indeed, most of Youssoufia’s rural areas feed on traditional wells. The main purpose of this chapter is to evaluate the degree of contamination of mine water along the pumping canal by fluoride. Wells located near this channel were also analyzed to see the influence of the existence of black phosphate in this region on these wells. At the end of this analytical part, it is obvious to conclude that the dewatering waters of the black phosphate mines of Youssoufia, known as dewatering water along the canal, contain significant fluoride concentrations in the order of 3–4 mg/l on average and the waters of the wells located near this canal have fluoride concentrations higher than the standard recommended by the National Office of Drinking Water in Morocco and the World Health Organization which is 1.5 mg/l. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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