Effective correlation time (τ) and volume ratio of paracrystalline (dense) (α1) and amorphous (α2) regions in an ultrathin PHB fiber containing Zn-ТFP.
\r\n\tBasic science studies have provided new insights into the pathophysiology of β-thalassemia. Studies of genotypic and phenotypic heterogeneity among patients and a better understanding of the control of erythropoiesis have provided new targets for designing novel agents that can be tailored to individual patient needs. JAK-2 kinase inhibitors and agents targeting the GDF-11/SMAD pathway are in clinical trials.
\r\n\r\n\tThis book will attempt to discuss the historical background of the disease and present the most up-to-date material regarding disease management in today's world for the reader to be updated on the best practice management of the disease.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"23abb2fecebc48a2df8a954eb8378930",bookSignature:"Prof. Akshat Jain",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10727.jpg",keywords:"History of Gene Mutation, Genetic Counselling, Anemia, Genotyping, Hemoglobin Electrophoresis, HLA typing, Hemolysis, Aplastic Anemia, Blood Transfusion, Laboratory Testing, Fetal Hemoglobin Modifiers, Gene Therapy",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 4th 2021",dateEndSecondStepPublish:"April 16th 2021",dateEndThirdStepPublish:"June 15th 2021",dateEndFourthStepPublish:"September 3rd 2021",dateEndFifthStepPublish:"November 2nd 2021",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a year",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"A board-certified pediatrician, in collaboration with Harvard Medical School, studied and reported the outcomes of a global hemophilia collaboration. Dr. Jain is a member of the American Board of Pediatrics, Hematology, and American Board of Pediatrics, also he is a Committee member for the American Society of Pediatric Hematology-Oncology, Special Interest Group in Global Pediatric Hematology oncology. Dr.Jain won the New York Academy of Medicine Honorary Associate Award.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"344600",title:"Prof.",name:"Akshat",middleName:null,surname:"Jain",slug:"akshat-jain",fullName:"Akshat Jain",profilePictureURL:"https://mts.intechopen.com/storage/users/344600/images/system/344600.jpg",biography:"Akshat Jain M.D. M.P.H.\n11175 Campus Street \nLoma Linda, California 92354\nPhone: (917) 331-3216\nakshatjainusa@gmail.com \n\nMEDICAL EDUCATION \n●\tS.S.R. Medical College, Belle Rive, Mauritius - MBBS, Bachelor of Medicine Bachelor of Surgery, 2007\n●\tPediatrics Residency Training ,The New York Medical College, Metropolitan Hospital , Dec2008-Dec 2011\n●\tPediatric Hematology Oncology and Stem Cell Transplant Fellowship, Cohen’s Children's Hospital of New York at LIJ-North Shore Health system. July 2012- September 2015\n●\tMaster’s in Public Health ,Hofstra University School of Public Health ,New York , August 2015\n\n\nHONORS/ AWARDS \n●\tThe New York Academy of Medicine Honorary Associate Award , December 2009\n●\tProgram Leadership Award - Committee of Interns and Residents (C.I.R./SIEU), April 2010\n●\tAmerican Academy of Pediatrics Program Delegate Award, New York Medical College, December 2010.\n●\tCitation of Honor from New York County for Excellence in Medicine and Service to Long Island, New York,Nassau county executive chambers , August 15,2015 \n●\tTimes of India N.R.I. ( Non Resident Achiever ) award , August 2015 \n●\tCertificate for academic excellence –Hofstra University School of Health Science & Human Services, New York August 26, 2015\n●\tAmerican Society of Hematology Leadership Institute Award , April 2016\n●\tGlobal Health Speaker Award , convener of Global Health Symposium, Hofstra NorthWell School of Medicine and School of Public health , May 2016\n●\tInternational Pediatric Lymphoma Meeting ,Session Chairperson of Pediatric Lymphoma , Indian Society of Hematology and Oncology , November 2016\n●\tContent Leader Award for Hematology perspective’s in the Global CoronaVirus Pandemic Preparedness Response for Medical Association of physicians of Indian Origin, April 2020.\n●\tConvener and Chairperson International Webinar for COVID 19 Coagulopathy, May 2020. \n●\tFeatured in the Top Doctors magazine 2020, ranked top pediatric Hematologist Oncologist for Southern California.\n\nNATIONAL/INTERNATIONAL POSITIONS \n●\tHofstra University Dean Advisory Board for the School of Health Professions, December 2017\n●\tEditorial Board – American Society of Pediatric Hematology Oncology Communications Committee, International Journal of Hematology Research (ISSN 2409-3548)\n●\tReviewer - JAMA Pediatrics (ISSN: 2168-6203), British Medical Journal (ISSN, 1468-5833), JAMA Oncology (ISSN: 2374-2437), International Journal of Hematology Research (ISSN 2394—806X), Journal of Pediatric Hematology and Oncology (ISSN: 1536-3678), New England Journal of Medicine (Resident 360). \n●\tMember – Core committee: American Cancer Society (A.C.S.) and American Academy of Pediatrics (A.A.P.) - Joint global pediatric Oncology taskforce.\n●\tAdvisor -World Health Organization, South East Asia for maternal and child health initiatives.( 2013-Ongoing) , Ministry of Health and Family Welfare ,Government of India ( 2014- Ongoing ) , American Academy of Pediatrics &American Cancer Society Global Taskforce on Pediatric Cancers.( 2014-Ongoing )\n●\tEditor – AAPI journal (American Association of Physicians of Indian Origin. Circulation -40,000)\n●\tVisiting Professorship in Hematology Oncology and Stem Cell Transplantation, Rajasthan University of Medical Sciences, India. ( 2009-Ongoing )\n●\tIndustry Advisor – Bayer, UniQure, Sanofi-Genzyme, Takeda, CSL Behring\n●\tDirector of International Bone Marrow Failure Consortium- India, part of the Global Hematology Initiative of Cohen Children’s Medical Center, New York, August 2015-2017. \n●\tCommittee member for the American Society of Pediatric Hematology Oncology Special Interest Group in Global Pediatric Hematology oncology. ( 2016- Ongoing)\n\n\n WORK EXPERIENCE \nNov 2017- Current Loma Linda University Children’s Hospital \n Director Division of Pediatric Hematology \n Director, Comprehensive Hemophilia Program\n Director, Comprehensive Sickle Cell Program \n Division of Pediatric Hematology Oncology and Stem Cell Transplantation\n Professor of Public Health, Loma Linda University School of Public Health \n\nMar 2017– Oct 2017 Pediatrics and Pediatric Hematology Oncology Practice \n Adventist Health Ukiah Valley, California \n\nSept 2015 –Aug 2016 Assistant Professor Pediatrics, Hofstra North Shore LIJ School of Medicine \n Section Head –Global Pediatric Hematology Oncology and Stem Cell Transplantation\n North Shore LIJ Health system.\n Associate Adjunct Faculty, Hofstra University School of Public Health.\n\nJuly 2012 – Sep 2015 The Steven and Alexandra Cohen’s Children's’ Hospital of New York at LIJ-North Shore \n Hofstra University - Pediatrics Hematology Oncology and Stem Cell Transplant Fellowship \n Chief - Jeffrey Lipton MD\n\nDec 2011- April 2012 Global Health : SMS Medical College and Group of Hospitals, Government of India \n Project Director for Project A.G.N.I. - Set up a regional Lead Poisoning prevention and \n anemia nodal center \n \n Course Director - Pediatric Subspecialty training module for Pediatricians at J.K. Lone \n Children’s Hospital for Government of India. \n\nDec 08- Dec 2011 The New York Medical College, Residency in Pediatrics \n Metropolitan Hospital, NY\n Maria Fareri Children's Hospital at Westchester.\n The Memorial Sloan Kettering Hospital. NY\n House staff on Stem Cell Transplantation service.\n \nApril – August 2008 Oklahoma State Medical Association (O.S.M.A.) Externship Program\n The Integris Baptist Teaching Hospital and Nazih Zuhdi Transplant Center\n\nRESEARCH EXPERIENCE \nNov 2017 – Ongoing: Current and ongoing – Director, Inherited Bleeding Disorder Experimental Therapeutics Program, Loma Linda University School of Medicine\nJan 2014 –July 2015 - Hofstra University School of Public Health \n Needs Assessment to barriers in cancer care for newly diagnosed patients in a resource \n Limited setting. \n Principal Investigator - Akshat Jain, Co-PI -Corrine Kyriacou \n\nJune 2012- July 2015 - Steven and Alexandra Cohen Children’s Medical Center \n Study – Non Invasive assessment of endothelial dysfunction in children with Sickle cell \n Disease. \n Co-Principal Investigator – Banu Aygun MD\n Study – Multicenter study assessing outcome of Reduced Intensity Conditioning for \n patients undergoing hematopoetic stem cell transplantation for Sickle cell disease . \n Co-Principal Investigator – Indira Sahdev MD\n \nJan 2012- Mar12 A.G.N.I. (Anterograde Growth Normalization Initiative) \n Project Director, Project of Government of India for establishment of Universal Lead \n Independent Pilot project to study effects of Elevated Blood Lead levels in children \n suffering from Developmental disorders- Adapted by W.H.O. 2014 for a National Level \n Lead Screening program, India \n \nJan 2009- Dec11 The New York Medical College, Metropolitan Hospital Center. NY\n Resident Physician – Hypothalamic volumes in patients with Growth Hormone deficiency.\n Maria Fareri Children's hospital / Dr.Richard Noto - Pediatric Endocrinology\n \nApril 2008-Dec 08 Nazih Zuhdi Transplant Institute, Integris Baptist Hospital, Oklahoma City\n Project – Single institution outcome study for Solid organ transplants\n Research Assistant Department of Hepatology\n \nOct 2007 – Dec07 Mount Sinai School of Medicine, New York, NY\n Project- Arterio-venous fistula post liver transplantation.\n Research mentor-Dr. Charissa Chang, Assistant Professor in Department of Liver Diseases. \n\nCERTIFICATION\n\n1.\tCalifornia State Medical License 8/2016- Present , New York State Licensure 8/2013-12/16\n2.\tAmerican Board of Pediatrics - Board certified, 11/14- Present\n3.\tAmerican Board of Pediatric Hematology Oncology – Board Certified , 06/2018- Present\n4.\tNeonatal Advanced Life Support 06/2009-Present \n5.\tPediatric Advanced Life Support 06/2009-Present \n6.\tECFMG Certification 12/2007-Present \n\nORAL PRESENTATIONS \n\n\n1.\tLeukemia and Lymphoma Society of America C.M.E. Symposium presentation – Leukemia and Beyond: Advances in Cancer Care and Blood Disorders in the 21st Century, October 2019\n2.\tLoma Linda University School of Medicine – Grand Rounds, Advances in the Management of Sickle Cell Disease, March 2019.\n3.\tLoma Linda University School of Medicine – Experimental Therapeutics in Sickle Cell Disease – New Horizons at Loma Linda , November 2018 .\n4.\tAdventist Health Ukiah , California - Neurological Defects of Iron Deficiency and Lead Poisoning in Humans , October 2017\n5.\tHofstra NorthWell School of Medicine - National Public Health Symposium on Global Public Health , Convener and Moderator ,April 2016 \n6.\tCleveland Clinic Children’s Medical Center, Ohio – Non BCR-ABL Myeloproliferative syndromes of childhood, January 19, 2016.\n7.\tChildren’s Hospital at SMS Medical College ,India – Pediatric Hematology Oncology Emergencies for the Tropics, November 13, 2015 \n8.\tHarvard Medical School, Boston Children’s Hospital Division of Pediatric Hematology – Advances in Global Hematology, Annual Hemophilia Twining symposium, August 2, 2015.\n9.\tNew York Medical College as Grand Rounds, Division of Pediatrics – Emergencies in Pediatric Hematology and Oncology, April 2015.\n10.\tMaurice A. 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Today, functional carriers of biologically active compounds and absorbents with a high specific surface area are widely used in biomedicine in the form of bioceramic minerals, polymer therapeutic systems, framework structures for cell engineering, nanoscale hybrid means of targeted drug transport, and a number of innovative systems that simultaneously function as implants and carriers of biologically active compounds [1, 2, 3, 4, 5]. Among these functional materials, the greatest practical and commercial advantages, in the near future, will be obtained by hybrid micro- and nanoparticles [6, 7], as well as composite ultrathin fibers [8, 9].
Micro- and nanoparticles based on biodegradable materials offer a wide range of applications as components of innovative forms or independent systems for drug delivery in the implementation of anti-inflammatory and antitumor therapy, wound healing, and thrombolytic therapy. The use of magnetic nanoparticles as part of innovative systems can facilitate targeted drug delivery, reducing the required dosage of a drug, and provide a prolonging effect of the activity of biological macromolecules, for example, enzymes, and the ability to visualize drug delivery processes [10, 11, 12].
The employment of biodegradable and biocompatible particles and fibers creates additional advantages in the development of a new generation of implanted therapeutic systems. Therefore, nowadays, the main part of the work aimed to develop biodegradable compositions in medicine is devoted to the creation of materials for tissue engineering. Modern metal implants (titanium and its alloys, stainless steel, etc.) are characterized by rigidity and endurance and do not cause an immune response but do not have the properties of osteoinduction and osteoconductivity. Often their application turns to add an additional surgical intervention to remove the implant. This increases additional risks and the duration of the patient’s recovery process, and the therapy aimed at restoring the bone tissue and its environment. Therefore, inorganic materials analogous to bone tissue, such as apatite and complex composite biodegradable forms that provide the transport of biological molecules and synthetic drugs, are objects of fundamental and applied research.
One of the innovative ways to obtain ultrathin fibers and fibrillar nanomaterials is the method of electrospinning (ES) of polymer solutions and melts [13, 14]. The development of technology for the formation of nanofibers in an electrostatic field makes it possible to create materials of various shapes and morphology with a high specific surface area and porosity, with adequate mechanical properties, and a wide range of structural, dynamic, and diffusion characteristics. Fibrillar matrices and mats formed by the obtained nanofibers create favorable conditions for free migration and proliferation of cells in the three-dimensional space of frame structures, and, accordingly, provide a high integration affinity of the material for living tissues of the body [15]. They are actively used in the design of biosensors, nanofilters, for wound therapy, to immobilize enzymes, in the creation of prolonged and targeted drug delivery systems, and other areas of modern biology and medicine [16, 17, 18, 19, 20].
It should be noted that in contrast to a great availability published data on the nanoparticles applications, the data on biodegradable and bioresorbable nanofibes is rather rare [21, 22, 23]. About a third of publications analyze the peculiarities of the ES technology, and the rest considers their characteristics, functional behavior
Biodegradable compositions are also applied in solving the problem of wound healing, which may include a set of subtasks—stopping bleeding, preventing inflammation, proliferation, and tissue reconstruction. Chronic wounds are characterized by high protease activity, infection, inflammation, and hypoxia [24, 25, 26, 27]. A wide range of wound healing materials is currently being developed. These are unfilled materials based on siloxysiloxane, dextran, urethane, collagen, etc.; materials including stem cells or vitamin E based on hyaluronic acid; materials based on extracellular matrix proteins (fibrin, fibronectin, collagen, etc.) for tissue reconstruction and angiogenesis; and materials including antibiotics and other drugs [28]. Materials in the form of films, hydrogels, foams, multilayer compositions, etc., have already received clinical use. Chitosan, known for its hemostatic and antibacterial activity, is used in some currently developed composite forms for accelerated wound healing and drug delivery for matrix formation and tissue reconstruction. In [29], chemically stable composite materials for wound coverage were based on two polysaccharides—cellulose and chitosan combining mechanical strength (cellulose) and the ability to stop bleeding, cleanse and heal wounds, deliver drugs, and overall bactericidal properties (chitosan).
It is known that the regeneration of cartilage tissue is directly related to the number of chondrocytes per unit of its mass, and the introduction of a suspension of chondrocytes into the damaged areas is currently considered a promising therapeutic approach. Foreign chondrocytes, being introduced into the joint cavity, do not cause a rejection reaction, because they have limited immunogenic activity. Much attention is now being paid to the development of composite hydrogels for injections—research is being carried out using photopolymerization, chemical crosslinking of molecules in the composition of the composite with carbodiimide, glutaraldehyde, genipin, and adipic dihydrazide. In the first case, the use of a photosensitizer and radiation is required, which limits the applicability of the approach, and in the case of crosslinkers, the main problem is their toxicity toward cells. In [30], a new representative of composite hydrogels was obtained based on chitosan and oxidized hyaluronic acid. The formation of the gel proceeded through the formation of a Schiff base between the amino and aldehyde groups of polysaccharide derivatives, N-succinyl-chitosan (S-CS) and hyaluronic acid aldehyde, and did not involve the use of a chemical crosslinking agent. The potential of using such composite hydrogels as scaffold structures for injections has been shown using the example of cartilage tissue cells in joints. In this study, the high content of chitosan led to a decrease in the rate of degradation of the composite.
Let us consider several examples of the use of composite particles based on biodegradable polymers. In [31], hydrogels based on chitosan and gelatin are used for long-term administration of the antiglaucoma drug timolol maleate and can reduce the side effects of its use. Hydrogels based on sulfonated chitosan and heparin-like chitosan (containing carboxymethyl and sulfate groups) increase blood clotting time [32], prevent protein and platelet adsorption on the membrane intended for blood purification [33], and prevent complement activation [34]. Hydrogels consisting of chitosan, heparin, and poly (γ-glutamic acid) with different ratios of components and loaded with superoxide dismutase were used to create a wound dressing with antioxidant properties [35], which had the potential to treat chronic trauma in diabetes and proved to be a promising wound healing agent. Heparin-loaded hydrogel based on photosensitive hydroxyethylchitosan promoted a long-term effect of lowering intraocular pressure after surgery to eliminate glaucoma [36]. While the possibilities of transporting the anticoagulant heparin as a constituent element of particles are being actively studied, a much smaller number of works are devoted to the transport of proteins associated with the functioning of fibrinolytic and anticoagulant systems—tissue plasminogen activator (tPA), streptokinase, and urokinase. The formation of complexes between enzymes and biodegradable polymers proved to be an effective way to overcome the short biological half-life of enzymes in the bloodstream, and the inclusion of magnetic nuclei in the particles revealed the potential of using biodegradable materials for targeted drug transport and diagnostics. Magnetic nuclei delivered on their envelope (for example, the composition of polyethylene glycol (PEG) and chitosan [37]) tPA or streptokinase promote thrombolysis controlled by an external magnetic field. Hydrogels based on chitosan and alginate with incorporated magnetic particles were investigated as carriers of the anticancer drug matrine for oral administration [38, 39]. The obtained systems provide pH-sensitive release and targeted delivery under the influence of weak magnetic fields. The inclusion of magnetic particles in systems based on hyaluronic acid allows to detect the processes of tissue regeneration and biological delivery of drugs with the participation of constructed systems [40].
The areas of possible application of biodegradable forms are not limited to the aforementioned examples. New designs of cardio stents with biodegradable or inert coatings are capable of providing targeted transport of such cardiac drugs as paclitaxel, sirolimus, tacrolimus, etc. These drugs are responsible for suppressing cell proliferation; therefore, their prolonged delivery significantly reduces the number of restenosis incidents as compared to the first generation of spring metal stents. Moreover, a nano-level modified stent surface for controlled cell adhesion is desirable. In urology, a separate group of polymer implants consists of representatives of natural biodegradable polymers—poly-α-hydroxy acids (polylactides and their copolymers) and poly-β-hydroxyalkanoates (polyhydroxybutyrate (PHB), and its copolymers with oxyvalerate, oxyhexanoate, etc.), and the base for neurological implants are biodegradable polymers such as polylactides or polyhydroxyalkanoates [41]. For urological applications, a prolonged release of bactericidal drugs is required, whereas for nerve tissue regeneration, a drug activates the development of a nerve impulse.
Modern works also include the creation of systems with a reverse response, an example of which is the form that releases insulin depending on the concentration of glucose in the blood [42]. The possibility of visualizing the area of development of the pathological process and monitoring the course of the treatment process is presented with the use of isotopes, fluorescent dyes, quantum dots, magnetic nanoparticles, and other markers [43]. Biodegradable innovative materials, thus, have received a wide range of possible applications in the treatment of various diseases (Figure 1) in the form of various medical forms—macroobjects, films, micro-, and nanoparticles, etc. A wide variety of required compositions and morphology of matrices of medical forms contributes to the fundamental and applied issues associated with the use of natural and synthetic materials for the delivery of low- and high-molecular-weight biologically active substances (BASs). More details on the possible chemical composition of matrices for drug transport and methods of drug inclusion in the matrix will be presented in the next section.
The main areas of pharmaceutical forms’ application for the delivery of low- and high-molecular-weight pharmaceuticals based on biodegradable macromolecules.
Let us consider the main components of biodegradable materials that make up innovative forms using the example of collagen, hyaluronic acid, carboxymethyl cellulose (CMC), chitosan, and other natural and synthetic macromolecules, the structural formulas of which are shown in Figure 2, most often used for bone tissue regeneration [43].
Structural formulas of some biodegradable macromolecules used for targeted transport of low- and high-molecular pharmaceuticals.
Chitosan is a polysaccharide of D-glucosamine and N-acetyl-D-glucosamine, linked by β (1 → 4) -glycosidic bonds. Chitosan is obtained by cleavage of the acetyl group from chitin. The deacetylation reaction can also be accompanied by the rupture of the glycosidic bonds of the polymer. The degree of deacetylation of chitosan and its molecular weight predetermines its reactivity and properties, causing the structural heterogeneity of macromolecules. The solubility of chitosan depends on the pH (it is insoluble at neutral values), and its salts, for example, chitosan hydrochloride and chitosan glutamate, are soluble at any pH.
The hydrophilicity of chitosan and its positive charge facilitate its reactions with negatively charged macromolecules and polyanions, which are both components of the biodegradable composite matrix and functional molecules.
This makes it possible to use sol-gel processes for drug binding. The positive charge of chitosan also promotes adhesion to the mucous membranes of the body, which makes it possible to use it for the transport of drugs through the mucous membrane. Thus, the features of chitosan are pH-dependent solubility (at pH <5 and basic pH) and insignificant toxicity due to ▬NH2 groups (it undergoes enzymatic degradation in vivo, and its degradation products are involved in the metabolic cycle). CMC can be used together with cellulose and is similar in structure to chitosan. The sodium salt of CMC is a water-soluble polymer. Cellulose is a polysaccharide with the formula (C6H10O5)n, in which the D-glucose residues are linked by β (1 → 4)-glycosidic bonds. Cellulose undergoes dissolution under the action of ionic liquids (organic salts, liquid at room temperature). In [29], such a solvent was used to obtain a composite material for wound dressings based on two polysaccharides – cellulose and chitosan.
Fibrinogen and fibrin are the next examples of protein molecules that can be components of micro- and nanoscale scaffolds. These proteins are present in the blood and are the main participants in the process of coagulation, which determines their high ability to interact with damaged tissues and cells. To solve problems associated with tissue regeneration, proteins can be modified or introduced into more complex systems, including, for example, growth factors or other proteins, as well as stem cells [44]. Fibrin gel formation can be initiated directly at the site of injury using particles on the surface of which thrombin is fixed [45].
The main protein of silkworm silk, fibroin, and the skeleton silk of the spider web, spidroin, have crystalline parts responsible for high tensile strength and amorphous parts that provide elasticity, which makes them versatile materials for use in tissue engineering, pharmacy, and medicine, regardless of the type of construction. The breakdown products of silk fibroin and spidroin are amino acids, which act as an additional building material for tissue regeneration [46].
Hyaluronic acid is a hydrophilic, non-immunogenic, biodegradable glucosaminoglycan—a polymer consisting of D-glucuronic acid and D-N-acetylglucosamine residues, linked alternately by β-1,4- and β-1,3-glycosidic bonds, which, in combination with other osteoconductive molecules, promotes bone growth. It has a high content in extracellular matrices, is a component of articular cartilage, and is part of the skin. Amphiphilic derivatives of hyaluronic acid promote its self-assembly in a core-shell nanogel for the transport of hydrophobic pharmaceuticals, e.g. anticancer.
For the transport of low- and high-molecular-weight therapeutic substances, “depot carriers” are used based on sodium alginate and its compositions with pectin, sodium hyaluronate, etc. Salts of alginic acid (alginates), in contrast to the polysaccharide acid itself, form colloidal solutions in water and have antimicrobial and hemostatic action.
Unlike natural macromolecules, synthetic biodegradable molecules such as poly-α-hydroxy acids such as hydrophobic polylactides (PLAs) and more hydrophilic polyglycolides (PGAs), as well as poly-β-hydroxyalkanoates (PHBs and its derivatives) do not elicit a biological response and are widely distributed as components of innovative forms for drug delivery. Degradation of polymers proceeds through hydrolysis of ether groups, and the rate and products of degradation are determined by the composition, structure, and molecular weight of molecules, as well as the content of ions and enzymes in biological fluids. Polymeric materials of the class of poly-β-hydroxyalkanoates or poly-α-hydroxy acids degrade to nontoxic products—CO2 and H2O [41]. Also commonly used are aliphatic polyesters, that is, polycaprolactones (PCLs). Blends of polymers or copolymers are often the basis for materials intended for the restoration of bone and cartilage tissue. The most popular copolymer is polylactide-co-glycolide (PLGA), the ratio of the components of which affects the hydrophilicity and biodegradability characteristics. During copolymerization, the degree of crystallinity decreases, as a result of which hydrolytic destruction proceeds faster [47]. Other common synthetic macromolecules for bone tissue regeneration are polypropylene fumarate (PPF), polyanhydrides, and polyphosphazenes [26]. Oligo(polyethylene glycol fumarate) (OPF) based on PEG is able to biodegrade, while PEG is not [48]. Degradation of PPF and OPF is due to the fumaric acid residue in the polymers. Copolymerization of macromolecules, for example, polyanhydrides, can be carried out to increase the hydrophobicity of materials and reduce the rate of their biodegradation. The combination of natural and synthetic materials in the compositions provides a wide range of properties of the systems and the possibilities of their use. An example of a natural material used for the transport of various drugs in the composition of composite forms is gelatin [49].
In innovative materials, the simultaneous use of natural and synthetic macromolecules creates unique opportunities for the delivery of various pharmaceuticals and ensuring the required release profiles. As in the case of synthetic ones, when using natural hydrogels, chemical and physical crosslinking of macromolecules allow one to regulate the diffusion of therapeutic substances included in biodegradable forms, and the biodegradation of macromolecules is also determined by the degree of their crosslinking and the type of crosslinking agent. In this case, the pharmaceuticals themselves can be covalently and non-covalently associated with biodegradable compositions, in particular, the inclusion of pharmaceuticals in the composition of Ca3(PO4)2 particles is carried out physically or chemically [24], and the release of pharmaceuticals can be controlled by the chemistry of Ca3(PO4)2, the porosity of the material, the surface area of the hydrogel particles, their charge surface, and crystallinity. In the case of covalent immobilization of macromolecular pharmaceuticals (for example, proteins), the release mechanism includes chemical/enzymatic cleavage of the active substance. The introduction of an antibiotic in the treatment of osteomyelitis can be provided by direct mixing of the drug powder with a bone graft or soaking the bone graft in an antibiotic solution [26]. Similarly, for the prolonged delivery of streptokinase, systems obtained by mixing the protein with chitosan were used [50]. Urokinase and streptokinase showed their activity as thrombolytics both on the surface and in the bulk of particles from chitosan and tripolyphosphate, providing delivery, and the indicators in both cases were higher than in the protein solution [51]. The introduction of pharmaceuticals into composite structures from a solution after their creation is one of the approaches that damage pharmaceuticals to the least extent. Chondrocytes in [30] were introduced into the hydrogel from a solution in which they were resuspended. Another example of a technique that provides a minimal effect on the drug structure is the approach using the state of a supercritical fluid, which provides a one-stage filling of porous matrices with medicinal substances. Approaches are known that include the formation of a special drug complex, for example, with cyclodextrins, for its use in a sol-gel process, during which biodegradable composite structures with pharmaceuticals incorporated into them are created [52]. Pharmaceuticals can also be adsorbed on the surface of implanted structures and coated with biodegradable polymeric materials to ensure their long-term release, which is realized, for example, in [25] during transfection. A hydrophobic drug can also be encapsulated in an oil core covered with a biodegradable shell, including, for example, chitosan [53]. Drug release can be divided by type into diffusion-controlled, controlled by chemical processes or matrix swelling, and controlled by external processes or devices.
Most of the listed approaches for the inclusion of pharmaceuticals in various matrices can also be implemented when nanoparticles are included in hydrogels. The particles are introduced into the compositions after the formation of the gel and at the stage of gel formation, with or without the use of covalent binding processes. Nanoparticles in the composition of hydrogels provide a change in their mechanical properties and swelling characteristics and are also able to impart magnetic, optical properties, electrical conductivity, and improved antimicrobial properties to systems [54]. Hybrid hydrogels may include, for example, carbon-based nanoparticles, inorganic particles, and nanoparticles of semiconductors, nanoparticles of metals and their oxides, polymers, and liposomes. For example, the introduction of magnetite nanoparticles into the hydrogel is provided due to their stabilization by oleic acid and the amphiphilic nature of the main component of the hydrogel-modified hyaluronic acid [40]. Pyrene ligands contribute to the formation of hydrogel particles with a “core/shell” structure. In this case, magnetic particles bound to thrombin were employed to form fibrin-based skeletal structures [45]. Solid colloidal nanoparticles can be the core for a polyelectrolyte shell deposited using layer-by-layer adsorption technologies [40], as well as be part of the shell itself, providing magnetically controllable particles. For example, the authors [55] modified hollow microcapsules obtained from dextran sulfate and poly-L-lysine with maghemite particles.
Thus, a large group of biological and synthetic macromolecules is used to create innovative forms for the drug delivery. Although a more detailed overview of the methods of drug encapsulation and biodegradable matrices composition cannot be presented within the required limits of this chapter, it is obvious that the chemical composition of materials combined with the features of medical forms created on their basis (which include characteristics such as size, porosity, the presence of covalent crosslinking, and stimulus sensitivity) and the method of drug encapsulation predetermine the different fate of biodegradable materials in biological media and different profiles of the release.
Among the biopolymers used in dentistry, traumatology, orthopedics, cellular engineering, surgery, along with polylactides, the most common is, probably, PHB, the main representative of the biopolymers of the polyhydroxyalkanoate family [56]. This biopolymer is a product of microorganisms’ biosynthesis. It has high biocompatibility, the ability to rapid biosorption without the formation of toxic products, and increased resistance to oxidative degradation [57, 58].
In many previous reports, the structure formation of fibrillar materials based on PHB-containing dipyridamole (DPD) [59], chitosan [60], titanium dioxide and silicon nanoparticles [61], iron (III)-chlorporphyrin complexes [62], etc. was considered. In these works, the influence of low-molecular-weight substances on the structure of the crystalline and amorphous phases of PHB fibers was shown. This section will present a review of the structure and properties of ultrathin PHB fibers obtained by ES, containing immobilized drug – dipyridamole (DPD).
The structure of intercrystalline regions in fibers containing drug is directly related to the state of the crystalline phase of the carrier polymer by the spatial organization of the pass-through chains [63]. The latter, in the case of a high degree of crystallinity, experiences deformation and conformational spatial difficulties. Therefore, it is necessary to distinguish two alternative situations, the first: when the degree of crystallinity is low and the distance between the crystallites and polymer lamellae is large, so that a relatively low concentration of drug is evenly distributed between polymer crystals and should have little effect on the conformation of uncrystallized polymer molecules. An alternative situation arises when conditions are created in highly crystalline polymers (such as PGB, PLA, and polyamide-6) to realize the maximum degree of crystallinity, for example, as a result of solvent plasticization or as a result of temperature annealing. In this case, the proportion of polymer segments included in noncrystalline regions is relatively small, the mechanical and diffusion behavior of the polymer is determined by the state of the elongated flow chains, and the concentration of the introduced drug, related to the volume of the intercrystalline phase, may exceed its thermodynamic solubility. Then the excess of the low-molecular-weight component is displaced from the polymer volume with the formation of an independent drug phase on the fiber surface, and the drug molecules remaining in the volume are potentially capable of influencing the conformation and dynamics of polymer molecules in the intercrystalline regions of the polymer.
The structure and molecular dynamics of these regions in biopolymer fibers can be effectively investigated by the electron paramagnetic resonance (EPR) method using the microprobe technique of stable nitroxyl radicals developed at the IHF RAS (Moscow, Russian Federation) [64]. The satisfactory agreement between the calculated and experimental results demonstrated earlier indicates, first of all, the effectiveness of the selected two-phase model of the intercrystalline space of the PHB fiber, which consists of more and less dense regions with corresponding different rotational mobilities of a stable radical in these regions.
An increase in the concentration of dense regions in the presence of a drug was observed for the composite system PHB-DPD. The corresponding calculations revealeded that the volume fraction of more dense regions in the intercrystalline space of PHB fibers is much higher than the content of less dense regions. Moreover, when pharmaceuticals are added to the fiber, it continues to grow insignificantly following the sequence 0.90 (0) < 0.93 (1) < 0.94 (3) < 0.95 (5), where the numbers in parentheses indicate the percentage of DPD mass concentration. This result seems quite natural if we take into account that the specific enthalpy of melting of PHB changes in the same sequence, reflecting, as in the previous case, the degree of its crystallinity.
As the concentration of the dense fraction in the intercrystalline regions of PHB increases, a corresponding decrease in the rotation rate of the radical is observed, and, therefore, the segmental mobility of macromolecules slows down. For the slow component of the rotational mobility, similar changes in the values of the correlation time in the fiber are observed, namely, the value of this dynamic parameter increases with an increase in the DPD content in the sequence 6.6 × 10−9 s (0) > 7.1 × 10−9 s (1) > 8.8 × 10−9 s (3) > 9.0 × 10−9 s (5%), which indicates a slowdown in the molecular mobility of the radical and, accordingly, a decrease in the molecular mobility of PHB chains in intercrystalline areas. The correlation time for the fast component in all samples, except PHB with 5% DPD (7 × 10−10 s), was 2.4 × 10−10 s, i.e. more than an order of magnitude lower than the previous values. Consequently, a change in the crystalline phase of the polymer affects the dynamics of chains in denser regions of the intercrystalline space and practically does not affect the fast component of their mobility in less-dense intercrystalline regions. These results can be explained within the framework of the model of the heterogeneous (binary) structure of intercrystalline regions of polymers with a high degree of crystallinity [65, 66]. The perfection of the crystal structure of nanofibers depends on the conditions of electrospinning, namely, on the rate of solvent desorption from the formed fiber and the temperature regime of its cooling [63]. Indeed, fragments of the polymer chain with a predominance of the straightened conformation are mainly involved in the formation of paracrystalline regions and the recrystallization of the polymer. Therefore, probe molecules with a correlation time τ in paracrystalline regions are sensitive to changes in the degree of crystallinity of PHB. On the contrary, the molecules of the same probe, located at a considerable distance from the crystals in regions with fast segmental mobility and approaching in their dynamic characteristics to the amorphous phase of the polymer, are practically unaffected by the crystalline phase of the fiber and, within some limits, retain their constant value.
During ES, as a result of difficult cooling and curing conditions of ultrathin fibers, their polymer structure can be far enough from the state of thermodynamic equilibrium. The imperfection of the crystalline phase and morphology is manifested in the insufficient orientation of the segments in the fiber, as well as in an atypically low degree of crystallinity [63]. Thermal annealing several tens of degrees below the melting point of PHB (annealing temperature 140°C) allows to sharply intensify segmental mobility and transfer the system to a more thermodynamically equilibrium state. Indeed, the time of thermal annealing at 2 h for PHB combinations with pharmaceuticals in the absence or low drug content for a number of samples significantly affects the rotation dynamics of the TEMPO radical. Whereas for highly crystalline fibers (with 3 and 5% DPD), this process has little effect on the rotational mobility of the probe, reflecting the segmental mobility of the chains (Figure 3).
Dependences of the effective correlation time (τ) on the annealing time at 140°C: 1—PHB, 2—PHB with 1%, 3—PHB with 3%, 4—with 5% DPD.
One of the possible mechanisms of PHB recrystallization upon thermal annealing of the fiber is that a part of the chain segments with a high degree of orientation β, which was acquired during the electrospinning process, reaches values greater than the critical value h/L ∼ √2/l, where h is the distance between chain ends, L is the persistent chain length, and l is the length of a single segment [67]. As a result, the sorption capacity of the fiber due to an increase in the degree of crystallinity decreases. Indeed, measurements of the concentration of a stable radical in the fibers also show a sharp decrease in this value after annealing for 2 h. For example, in the initial PHB fibers, the concentration of the radical after absorption from vapors was 8 × 1015 spin/g, while this value after annealing for 2 h decreased to 1.4 × 1015 spin/g. A similar picture was observed for other biopolymer fibers containing a porphyrin complex.
The correspondence is observed between the content of the crystalline phase of PHB (structural characteristic) and the value of the correlation time (dynamic characteristic), so that molecular mobility decreases as the total volume of intercrystalline regions decreases due to an increase in crystallinity of PHB and, consequently, the involvement of an increasing number of mobile polymer segments in dense polymer regions with low mobility and high values of τ. Obtained results allow to conclude that, in the presence of a drug, from a PHB solution by ES, ultrathin fibers of various geometries with structures of various degrees of equilibrium and perfection are formed, which is true both for the crystalline phase and for intercrystalline regions, where redistribution between the amorphous and paracrystalline states of PHB is possible. The nonequilibrium of intercrystalline regions for PHB with the absence or low content of biologically active substances (DPD) is confirmed by a change in the rotational mobility of a stable radical and an increase in crystallinity. All results, including the effect of drug concentration on the fiber shape and its dynamic characteristics, are in good agreement with the thermophysical parameters of the system and should be directly applied if describing the directed and prolonged transport of bioactive compounds.
A natural continuation of these studies is the transition from the structural characteristics of ultrathin fibers to the study of the diffusion kinetics of a drug in their bulk. In the next section, the results of the dependence of diffusion transport as the main process responsible for controlled drug release on the geometric dimensions of the fiber, its crystallinity and the porosity of fibrillar films will be presented. The obtained results will be used to consider diffusion kinetics, which, in combination with the analysis of segmental dynamics, represent two fundamental processes that determine the rate and mechanism of controlled drug release from fibrillar therapeutic systems.
The process of controlled targeted delivery of biologically active substances, for example, anti-inflammatory and antidiabetic pharmaceuticals or growth hormone [68, 69, 70], cannot be adequately described without considering their diffusion. In this regard, despite the impressive technological advances in the creation of ultrathin polymer fibers for various applications, the solution of diffusion and enzymatic-hydrolytic problems in the systems monofilament—biologically active substance (BAS) and fibrillar matrix—BAS is found in an extremely limited number of works (e.g. [71, 72, 73]) and requires in-depth analysis both experimental and theoretical levels. Consideration of the earlier-mentioned diffusion-kinetic problem was carried out using the example of ultrathin fibers with an encapsulated drug. Combining the results of transport in fibers and fibrillar membranes with the structural and dynamic characteristics of a biopolymer carrier, a consistent controlled release model is proposed that satisfactorily describes the combination of BAS diffusion and hydrolysis kinetics in an innovative therapeutic system based on a typical biodegradable polyester (PHB).
In Figure 4, typical kinetics of the release of dipyridamole (DPD) from fibers of different geometry consisting of ellipse-like and cylindrical structures and with different drug concentrations is plotted. As in the case of the “monolithic PHB film—drug” system [74], for the fibrillar matrix formed by ultrathin PHB fibers, the kinetic release profiles have two characteristic kinetic regions of linear and nonlinear form. The bimodal nature of controlled release is especially pronounced for fibers with a higher DPD content in the fiber (3 and 5 wt%). Under our proposed model, the initial nonlinear section mainly reflects a diffusion process with a characteristic drug diffusion coefficient, while the linear region corresponds to a kinetic process reflecting fiber degradation with partial loss of its mass. Briefly, the essence of this process is determined by the onset of hydrolysis of the ester functional groups of PHB. In the process of hydrolytic destruction, the drug encapsulated in the fiber passes into the surrounding aqueous solution not only as a result of diffusion but also as a result of partial fiber disintegration by the mechanism of surface destruction or erosion [75].
Typical kinetic profiles of controlled release of DPD from PHB fibers. The concentration of DPD is 1 (1), 3 (2), and 5 wt% (3). scanning electron microscopy (SEM) photomicrographs illustrate the shape of the fibers; magnification 1000×.
In kinetic measurements, the fiber sample was immersed in a 60% aqueous solution of ethanol and the optical density of DPD samples was determined with a periodic sampling. The interval of sampling depended on the fiber composition and, accordingly, on the rate of drug release; it was from 1 to 30 min. The experiments lasted from several hours to several days. Termination of an increase in the optical density of DPD exhibiting two characteristic peaks at λ = 410 nm and a more intense peak at λ = 292 nm with an extinction coefficient of 31,260 L/(mol × cm) indicated that the drug release was completed.
With this formulation of the problem, the kinetic profile of drug release is described by the following system of equations. During the time interval Δt, the cumulative mass of the drug released from the fibrillar film by the time t (ΔMd(t)) is the sum of two terms: the amount of drug that entered the solution volume by the diffusion mechanism (ΔMD) and the amount of the drug that passed into solution as a result of partial loss of fiber mass ΔMf, which contained ΔMk grams of drug immobilized by polymer molecules and incapable of diffusion in a polymer medium. The above reflects a simple balance of the change in the mass of the active component in the fiber, which reflects the Eq. (1);
With a constant volume of the surrounding solution V and intensive stirring, external diffusion restrictions can be neglected. In this case, for a fibrillary film, by analogy with a monolithic nonporous film [75], one can write a differential equation showing the simultaneous contribution of drug diffusion and PHB hydrolysis by the zero-pillage mechanism:
where Сd and Gd are the total concentration of the drug that entered the external volume V by the time t and the concentration of the mobile drug fraction capable of diffusing in the polymer sample with the corresponding effective diffusion coefficient Deff, independent of the coordinate and time, and kh is the fiber mass loss constant, mainly due to the hydrolysis of the ester groups of PHB.
In a fibrillar film formed by a random interlacing of ultrathin fibers, Deff is determined by two coupled processes: the diffusion mobility of drug molecules in the fiber volume (Df) and its diffusion transport in the interfibrillar space filled with a solvent (Dw). Consequently, the total transfer can be approximated by the model of a pseudo-two-layer medium. Following the models of Crank [76] and Mackey-Mears [77], the relationship between the effective diffusion coefficient (Deff), individual diffusion constants (Df, Dw) and the geometric characteristics of the system (LM, Rf and Lw) has the form:
here Rf and Lw are the average characteristic dimensions of the length of the diffusion path of the drug in the fiber and interfiber space, respectively, and LM is the thickness of the fibrillar film.
Taking into account the symmetry of the film during double-sided desorption, its size and fiber diameter are divided by 2. For a cylindrical fiber, the length of the diffusion path is determined by its radius, while for Lw, we used a correction for the increase in the diffusion path due to the bending of the drug molecule around randomly arranged cylindrical fibers. The correction for impenetrable obstacles was first introduced in the classical work of Mackey and Mears [77] and was recently used to describe transport in a magnetic composite based on chitosan and PHB [78]:
where φf is the volume fraction of polymer fibers in the fibrillar film, the values of which, as well as the average radii, are given earlier in Table 1.
[Zn-ТFP] % | τ 1010 s | τ 1010 s, annealed at140 0С | α1/α2,*% | ∆НM, J/g | αс, % | ||
---|---|---|---|---|---|---|---|
Dense area | Amorphous area | Dense area | Amorphous area | ||||
0 | 80.7 | 5.7 | 73 | 6 | 3.1 | 86 | 61 |
1 | 107 | 6 | 57 | 7.5 | 6.2 | 93 | 65 |
3 | 117 | 6.1 | 59 | 7.9 | 11 | 94 | 66 |
5 | 125 | 6.9 | 58 | 8.1 | 19 | 96 | 68 |
Effective correlation time (τ) and volume ratio of paracrystalline (dense) (α1) and amorphous (α2) regions in an ultrathin PHB fiber containing Zn-ТFP.
Subscripts 1 and 2 refer, respectively, to more dense (paracrystalline) and less dense (amorphous) regions of the intercrystalline space. ∆НM—specific heat of fusion and αс—degree of crystallinity of PHB.
Taking into account the introduced correlation of the diffusion path length in the aqueous phase, and also taking into account the correction for the degree of crystallinity of the polymer Fc = (1–αc), proposed in monograph [79], Eq. (4) takes a more detailed form:
allowing you to go to the comparison of the contribution of two processes that determine the total transfer process, namely, drug diffusion in the fiber and diffusion in the aqueous interfibrillar space of the PHB film. A preliminary estimate of the values of the diffusion coefficients of the drug in PHB (Df) showed that they are several orders of magnitude lower than the corresponding coefficient in the aqueous interfibrillar space, the last term on the right-hand side of Eq. (5) becomes much less than the first, which leads to a simplification of the sought expression for the diffusion coefficient of the drug in the hospital:
where the geometric (φf, LM) and structural (Fc = 1 – αс) characteristics were determined using the SEM and differential scanning calorimetry (DSC) data, respectively.
Simplification of Eq. (5) to expression (6) is possible only if the limiting stage of drug desorption from a fibrillar film of thickness LM is its diffusion in the polymer medium of the fiber. This is not universal, since with an increase in the volume of the interfibrillar space of the system, i.e. with a decrease in the proportion of fiber and its less dense packing, as well as with an increase in the concentration of hydrophilic groups in the polymer, i.e. with an increase in their affinity for a polar solvent (for example, for water) and a corresponding increase in Df, it is possible to take into account both terms, the values of which can be quite comparable.
The diffusion equation for an infinite cylinder which satisfactorily approximates the shape of the fiber and provided that the drug at the initial moment is uniformly distributed over the volume of the polymer was presented by Crank in his classic work [76]:
where r is the radial coordinate of diffusion, and the symbol Gd, as in Eq. (2), denotes the concentration of the mobile fraction of the drug in a cylindrical fiber with a corresponding constant diffusion coefficient Df and Rf as before denotes the average radius of the fiber. The initial and boundary conditions corresponding to drug desorption from a cylindrical fiber are as follows: Gd = G0d at t = 0 (at the initial moment of time) and under the condition 0 < x < Rf:
Gd = 0 at r = R (at the fiber-solution interface) and under the condition t > 0.
The second boundary condition is written from considerations of symmetry and indicates the absence of flux at the center of a single fiber ∂Gd/ ∂r = 0 at r = 0.
It was shown in [80] that the solution of Eq. (7) has the form of a power function and makes it possible to obtain the dependence of the cumulative amount of pharmaceuticals coming from the fiber into the environment by the diffusion mechanism ΔMD(t) on its contact time with this medium t:
where ΔMD∞ is the limiting value of ΔMD under the condition t → ∞.
Note that Eqs. (7) and (8), describing the diffusion of drug through the side walls of an infinite cylinder, are valid provided that the length of the fiber exceeds its radius by at least five times [81], and this requirement is strictly fulfilled for fibers of practically infinite length, obtained by the technology of electrospinning. In addition, the last equation is valid provided that the inequality ΔMD/ΔMD∞ < 0.4. The combination of Eqs. (2) and (8) gives the final expression for the release of the drug from the cylindrical fibers, both taking into account the weight loss during hydrolysis and due to the diffusion of the drug:
where kc = kh - [Df/Rf2]. The positive sign in the equation shows that under the given conditions for PHB, the inequality kh > [Df/Rf2] is fulfilled.
The experimental curves shown in Figure 4 correspond to Eq. (9), which allows the calculation of the fiber diffusion coefficients Df. For calculations, these drug release curves were presented in diffusion coordinates ΔMD/ΔMD∞ ∼ t1/2, as shown in Figure 5. Comparison of the experimental results presented in Figure 3 with the corresponding symbols, and calculations according to Eqs. (7) and (9), shown by solid lines, indicates their good agreement and demonstrates the possibility of using this model to assess the diffusion characteristics of ultrathin cylindrical fibers. Table 2 exhibits the concentration of mobile СD∞ and immobilized Сh∞ drug fractions.
Kinetic curves of DPD release from PHB fibers, presented in diffusion coordinates. The concentrations of DPD are 1 (1), 3 (2), and 5 wt.% (3); LM is the total thickness of the fibrillar film.
DPD, wt % | Rf × 104, cm2 | Df × 1012, cm2/s | СD∞ × 102, g/g | Сh∞ × 102, g/g | kc × 105, s−1 | kh × 105, s−1 |
---|---|---|---|---|---|---|
5 | 1.6 | 1.5 | 3.35 (53%) | 1.65 (34%) | 4.4 | 1.4 |
3 | 2.5 | 3.2 | 1.8 (56%) | 0.89 (32%) | 6.1 | 1.1 |
1 | 9.8* | 6.9* | 0.78 (78%) | 0.22 (22%) | 9.4 | 8.5* |
Sorption, kinetic, and diffusion characteristics of the PHB-DPD fiber system. Concentration of mobile СD∞ and fixed Сh∞ fractions of DPD in fiber; СExt—concentration of DPD in the interfiber space. The percentages of each fraction are indicated in parentheses.
The conditional calculations of the corresponding characteristics, calculated approximating the ellipsoids of revolution with cylinders of larger diameter.
The effect of a sharp drug release at the initial portion of the kinetic curves is called the “burst effect” [82]. In our case, it is mainly associated with the residual drug concentration displaced from the fiber volume during the electrospinning process. The appearance of this fraction does not exceed 10% and is observed only for ultrafine fibers with a high drug loading (> 3%). When the sample is immersed in an aqueous medium, it is removed from the film due to rapid diffusion mobility in the hydrated interfibrillar space. It should also be noted that the concentration of mobile drug molecules decreases with an increase in crystallinity and therefore reaches a maximum value for fibers containing 1% DPD, having the lowest crystallinity of 38%. The last line of Table 2 shows the constants of the drug yield due to the loss of fiber mass during hydrolysis (kh). It can also be noted here that the rate of hydrolysis decreases with an increase in the crystallinity of the fiber and the lower, the higher the concentration of the drug in the fiber.
The totality of the results known in the literature and presented in this chapter allows us to draw two conclusions. First, the intercrystalline regions of ultrathin PHB fibers have a close packing of chains, which is significantly higher than the density in the amorphous region of the film, which is confirmed by EPR measuring. Second, under the same conditions, the values of drug diffusion coefficients in ultrathin and highly crystalline PHB fibers, as well as in its spherical microparticles containing DPD [83], are several orders of magnitude lower than similar characteristics measured for PHB films.
Over the past 15 years, there has been not only significant progress at the level of theory and modeling of the processes of directed transport of biologically active compounds, but at the same time a large number of polymer and hybrid materials were created for modern therapy, providing an innovative component for drug delivery. Today, the main trend is the accumulation of experimental data showing how nanotechnological processes, including electrospinning, affect the characteristics of the developed means of targeted drug delivery.
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Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:245,paginationItems:[{id:"196707",title:"Prof.",name:"Mustafa Numan",middleName:null,surname:"Bucak",slug:"mustafa-numan-bucak",fullName:"Mustafa Numan Bucak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196707/images/system/196707.png",biography:"Mustafa Numan Bucak received a bachelor’s degree from the Veterinary Faculty, Ankara University, Turkey, where he also obtained a Ph.D. in Sperm Cryobiology. He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. 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Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. Since 2014 she has been responsible for the Clinical Analysis Laboratory of the CEU-Cardenal Herrera University Veterinary Clinical Hospital.",institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"439435",title:"Dr.",name:"Feda S.",middleName:null,surname:"Aljaser",slug:"feda-s.-aljaser",fullName:"Feda S. 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The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11418,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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