Plastic (petroleum and plant-derived polymers) and natural matrices analyzed in this study.
\r\n\trescue missions especially in difficult to access areas. Precise control of aerial robotic systems with multiple degrees of freedom arms is a challenging task due to the fact that the translational and rotational dynamics of the aerial vehicle are strongly coupled with the dynamics of the manipulator. In order to accomplish complex missions in presence of uncertainties in the environment, to achieve better maneuverability and precise 3D position and attitude control, nonlinear control techniques have been found effective. Swarm robotics (multiple robot working together) is another exciting application of the aerial robotics. This book intends to provide a wide range of readers in applied mathematics and various engineering disciplines an excellent survey of recent studies of aerial robotic systems.
",isbn:"978-1-78984-567-9",printIsbn:"978-1-78984-566-2",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"53805f091c3107536edd2579c9987649",bookSignature:"Dr. Mahmut Reyhanoglu and Dr. Geert De Cubber",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7792.jpg",keywords:"Nonlinear Dynamics, Lagrangian Formulation, Visual Tracking, Way Point, Lyapunov Technique, Backstepping, Surveilance, Emergency Response, Crop Monitoring, Sliding Mode Observer, Nonlinear Filter, Coordinated Control, Leader-Follower",numberOfDownloads:1023,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 11th 2018",dateEndSecondStepPublish:"January 15th 2019",dateEndThirdStepPublish:"March 16th 2019",dateEndFourthStepPublish:"May 21st 2019",dateEndFifthStepPublish:"July 20th 2019",remainingDaysToSecondStep:"a year",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,editors:[{id:"15068",title:"Dr.",name:"Mahmut",middleName:null,surname:"Reyhanoglu",slug:"mahmut-reyhanoglu",fullName:"Mahmut Reyhanoglu",profilePictureURL:"https://mts.intechopen.com/storage/users/15068/images/system/15068.png",biography:"Mahmut Reyhanoglu is presently the Glaxo Wellcome Distinguished Professor of Engineering at the University of North Carolina at Asheville, North Carolina, USA. His extensive research makes use of advanced mathematical techniques and models that arise from fundamental physical principles. His major research interests are in the areas of nonlinear dynamical systems and control theory, with particular emphasis on applications to mechatronics and aerospace systems. He has edited 3 books, and authored/co-authored several book chapters and over 130 peer-reviewed journal/proceedings papers. He served on the IEEE Transactions on Automatic Control Editorial Board and on the IEEE Control Systems Society Conference Editorial Board as an Associate Editor. He also served as International Program Committee member for several conferences and as a member of AIAA Guidance, Navigation, and Control Technical Committee. 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Geert’s main task is to apply computer vision techniques to mobile robots, rendering these robots able to perceive, analyze, and – to some degree – understand their environment.\nGeert was the coordinator of the EU-FP7-ICARUS projectnwhich was a large-scale EU-project dealing with the development of unmanned tools (aerial, ground and marine robots) which can assist search and rescue workers to save human survivors after a major crisis (earthquake, tsunami, typhoon, shipwreck, etc.).",institutionString:"Royal Military Academy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"242",title:"Aerial Robotics",slug:"aerial-robotics"}],chapters:[{id:"67435",title:"A System for Continuous Underground Site Mapping and Exploration",slug:"a-system-for-continuous-underground-site-mapping-and-exploration",totalDownloads:136,totalCrossrefCites:0,authors:[null]},{id:"67297",title:"Decentralised Scalable Search for a Hazardous Source in Turbulent Conditions",slug:"decentralised-scalable-search-for-a-hazardous-source-in-turbulent-conditions",totalDownloads:137,totalCrossrefCites:0,authors:[null]},{id:"67003",title:"Vision-Based Autonomous Control Schemes for Quadrotor Unmanned Aerial Vehicle",slug:"vision-based-autonomous-control-schemes-for-quadrotor-unmanned-aerial-vehicle",totalDownloads:162,totalCrossrefCites:0,authors:[null]},{id:"67705",title:"Advanced UAVs Nonlinear Control Systems and Applications",slug:"advanced-uavs-nonlinear-control-systems-and-applications",totalDownloads:312,totalCrossrefCites:0,authors:[null]},{id:"68391",title:"Robotic Search and Rescue through In-Pipe Movement",slug:"robotic-search-and-rescue-through-in-pipe-movement",totalDownloads:280,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194666",firstName:"Nina",lastName:"Kalinic Babic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194666/images/4750_n.jpg",email:"nina@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"65255",title:"Elemental Analyzer/Isotope Ratio Mass Spectrometry (EA/IRMS) as a Tool to Characterize Plastic Polymers in a Marine Environment",doi:"10.5772/intechopen.81485",slug:"elemental-analyzer-isotope-ratio-mass-spectrometry-ea-irms-as-a-tool-to-characterize-plastic-polymer",body:'\nSince 1950, the production and use of plastics has been constantly increased reaching a global production of 280 million tons in 2016 (i.e., as thermoplastics and polyurethanes), with China as the major producer (29%) [1].
\nPlastics represent a group counting hundreds of different materials derived from fossil sources (e.g., oil and gas) among which the most produced are polypropylene (PP), high- and low-density polyethylene (HDPE, LDPE), polyvinyl chloride (PVC), polyurethane (PUR), polyethylene terephthalate (PET), and polystyrene (PS). Due to their high versatility, durability, low weight, and low cost, plastic materials find applications in almost any market sector, but primarily in packaging (39.9%) and building industries (19.7%) [1].
\nIn recent years, the growing evidence about the massive presence of plastic litter in the ocean, its pressure on the marine environment and wildlife, and its impact on marine-related human activities (such as fishery, shipping, and tourism) has raised lot of attention in the scientific, regulatory, and civil communities (Figure 1).
\nPathways through which litter reaches the sea (illustration by Davide Zanella).
Oceanographic surveys have recorded the presence of plastics in any geographical regions, including remote polar areas, and at any depth, from the sea surface to the seafloor of the oceans (Figures 2–4).
\nMarine litter on the beach (photo by Tomaso Fortibuoni).
Seabird nesting on plastic nets (public domain).
Tangle of fishing nets on a beach (photo by Francesca Ronchi).
The amount of plastic debris in the sea is still unknown due to the large variability of its distribution as regards both spatial and temporal scale, which prevents accurate estimates. However, modeling studies have recently approximated that 5–13 million tons of plastics (i.e., equivalent to 1.5–4% of global plastic production) end up in the oceans every year [2].
\nThe slow degradation rates of plastics under environmental conditions provide additional complexity to this global issue, by contributing to their accumulation in all terrestrial and aquatic environments. It has been estimated that, once in the ocean, the majority of manufactured polymers persist for decades and probably for centuries due to their low degradability (Figure 5) [3, 4].
\nEstimated decomposition times of different types of garbage dispersed in the marine environment (illustration by Davide Zanella).
In both terrestrial and marine environments, degradation of petroleum-derived plastics occurs through abiotic and biotic processes (i.e., UV degradation, hydrolysis, and decomposition by microorganisms), leading to their fragmentation into increasingly smaller pieces. Thus, plastic particles dispersed in the environment are commonly divided into three main classes based on their size: macro: >25 mm, meso: 5–25 mm, and microplastics: <5 mm. The smaller-size class, which includes both primary microplastics (i.e., particles produced as such, e.g., plastic pellets, exfoliating cosmetics, or synthetic clothing fibers) and secondary particles (i.e., particles derived from the breakdown of larger plastic debris), is likely to be the most abundant in the ocean today [5].
\nThe concern about the heavy contamination of the marine environment by plastics is related to the potential of plastic debris to cause harm to the inhabiting organisms via different mechanisms. Among the most alarming issues, there is an uptake and a bioaccumulation of plastic debris by marine organisms at almost all levels of the food web and the consequent trophic transfer. Recent studies have reported that micro and nanoplastics can easily be taken up and ingested by marine organisms (i.e., zooplankton, worms, bivalves, crustaceans, demersal and pelagic fishes, seabirds, reptiles, and mammals), resulting in a significant impact on the aquatic wildlife and possibly on human health via seafood consumption [6]. Furthermore, due to the large surface to volume ratio, microplastic fragments can potentially adsorb many kinds of common marine contaminants on their surface, in particular hydrophobic organic substances such as polychlorinated biphenyls, polyaromatic hydrocarbons, and organochlorine pesticides [7, 8]. This can promote their transport in the environment and induce toxic effects following ingestion and desorption (e.g., endocrine disruption, mutation, and cancer). Moreover, another source of concern is the possible release of additives commonly present in plastic formulations (i.e., bisphenol A, phthalates, and flame retardants) [8, 9], and although the leaching rates of these common additives in seawater are poorly known, their potential for toxicity is considered to be very high.
\nSeveral actions have currently been undertaking at national and international levels to tackle the contamination of marine environments by plastics. Their main aim is to achieve a general reduction of plastic use (in particular packaging and disposable items), recycling of plastic items at the end of their lifetime, and replacement of the use of plastics with more sustainable materials and biopolymers (e.g., plant-derived polymers [10]), which are more prone to degradation by microorganisms and show a shorter persistence once dispersed in the environment.
\nWith the growing evidence of the severe impact caused by plastics on the wildlife, the assessment of the presence, behavior, and fate of plastics in the marine environments has become a fundamental research issue, highly advocated to the scope of putting in place more effective policies. However, especially for the smallest particles (i.e., microplastics), their efficient identification to the scope of assessing the plastic load in the environmental compartments (e.g., seawater, sediments, and biota) is a serious challenge for scientists. Many analytical techniques have been used to identify plastic debris in environmental samples, as largely reviewed in the literature [11, 12]. Among the most used approaches, there are electron scanning microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS, ESEM-EDS), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR) [13], and thermal analysis (pyro-GC/MS). Other analytical methods used to identify plastic materials are near infrared spectroscopy (NIRS), differential scanning calorimetry [14], and UV-VIS spectroscopy [15, 16].
\nStable isotope analysis, which is an analytical technique that measures the relative abundance of stable isotopes yielding an isotope ratio that can be used as a research tool, is finding application in a growing number of different research fields and practical case studies. For instance, it is widely used to trace the origin of organic matter in various environments [17, 18], to track fraud in the food industries [19] and to identify microtraces of drugs, flammable liquids, and explosives in forensic cases [20]. This technique has been only rarely applied to assess the presence of microplastics in environmental samples [21]. Its potential for detecting plastic debris in environmental samples relies on different isotopic signatures of carbon in (i) petroleum-derived materials, (ii) C4 plants used in the synthesis of bioplastics, and (iii) marine samples’ matrices (e.g., particulate organic matter, plankton, tissues of marine organisms, algae, and marine plants).
\nThe term isotopes (from the Greek iso, same and topos, place) identifies atoms of the same chemical element, that is, the same place in the periodic table of the elements, that has the same atomic number but different atomic mass number. In other words, isotopes are atoms having the same number of protons and electrons (equal chemical properties) and a different number of neutrons (different physical properties). Each element has known isotopic forms, and in total, there are 275 isotopes of the 81 stable elements, in addition to over 800 radioactive isotopes (Figure 6).
\nStable isotopes have a proton/neutron ratio lower than 1.5.
Isotopes of a single element possess almost identical properties. They are commonly classified as natural or artificial, stable, or unstable. The quantification of the ratio between two isotopes allows to determine if two chemically similar environmental samples have different origins, related to the difference of the original sources. The isotopic distribution characterizing the sources may be influenced by phenomena of a different nature, which in turn may cause significant variations in the final products.
\nDepending on the chemical element, variations in the relative mass abundance of its isotopes can be detected through the analysis of stable isotopes. Technological advances in isotope analysis have led to the development of scientific instruments able to measure very small variations in the abundance of stable isotopes with high precision and accuracy (mass spectrometry). Therefore, stable isotope analysis can be applied considering different elements, thus giving nowadays applications in different fields of science.
\nFor a given chemically stable element, its isotopic composition in a sample (R) is equal to the ratio between the abundance of the heavy isotope with respect to the light one (e.g.,13C/12C), and it is expressed as deviation, in parts per thousand, from an international reference standard material (δ‰), according to the equation (Eq. (1)) given below:
\nwhere Rsample is the mass ratio of the heavy isotope to the light isotope measured in a sample and Rstandard is the isotopic ratio defined for the standard. The standard reference material that is commonly used for carbon is Vienna Pee Dee Belemnite. Thus, positive δ values indicate that the heavy isotope is enriched in the sample compared to the standard, while negative δ values indicate that the heavy isotope is depleted in the sample.
\nThe possibility of distinguishing two samples on the basis of their relative abundance of two isotopes bases on the phenomenon of isotopic fractionation, which can be enacted by a wide range of chemical (e.g., nitrification and ammonification), physical (e.g., evaporation and condensation), and biological (e.g., photosynthesis, assimilation, and excretion) processes. In fact, many natural (and anthropic) processes can alter the isotopic signature of a chemical element in a matrix by causing an imbalance of the isotope distribution that leads to a variation of its original isotopic signature [22]. Thus, as the extent of fractionation of many chemical elements have been proved to be sensitive to specific processes/variables, it can be used as a tool to investigate the involved process/variable itself. In general, two mechanisms of isotopic fractionation can be distinguished:
Thermodynamic, that is, due to a difference in bonding energy of the isotopes in the compounds. This mechanism implies that:
heavy isotopes accumulate in oxidized products;
the isotopic fractionation is favored at low temperatures, since at high temperatures, the differences between the isotopes are attenuated;
the process is not relevant in the case of chemical reactions of gaseous substances and biological reactions.
Kinetic, that is, due to different reaction rates of the isotopes. In this type of mechanism, it is generally observed that fast, irreversible, and unidirectional processes are favored. This is the case of most of the biological processes, where lighter isotopes are preferentially used, as their employment requests less energy. It also occurs when the products are easily removed from the reagents, in processes such as evaporation, diffusion, etc. These processes are featured by:
the preferential breaking of the bonds formed by light isotopes;
the preferential distribution of light isotopes in products and of the heavy ones in the reagents.
Given a chemical substance AB characterized by the presence of a certain isotopic distribution of element X, we can calculate the fractionation factor by dividing the ratio of the number of isotopes X in product A with the ratio of the number of isotopes X in product B (Eqs. (2) and (3)).
\nwhere
\nHowever, the fractionation factor (α) is normally replaced by the isotopic enrichment factor (ε), which is defined as (α − 1) × 1000.
\nCarbon and nitrogen isotope analysis is used to investigate the trophic web and the matter flows among the main components of an ecosystem (e.g., organic matter, producers, primary and secondary consumers); it can be used to understand chemical and biological processes occurring at both ecosystem and organism levels. Stable isotope analysis can also be a useful tool for assessing the origin of water, atmospheric, and soil pollution.
\nThe two main carbon reserves in nature are represented by organic and inorganic carbon, which are characterized by different isotopic fingerprints due to the different processes in which they are involved (Figure 7). The inorganic carbon (carbonate) is involved in the exchange equilibrium among (i) atmospheric carbon dioxide, (ii) dissolved bicarbonate, and (iii) solid carbonate. The exchange reactions among these three forms lead to an enrichment of the heavy isotope in the solid carbonate form (δ13C equal to 0‰). In contrast, the kinetic reactions which mainly involve the organic carbon (i.e., photosynthetic process) determine a concentration of the lightest isotope in the synthesized organic material (δ13C equal to about −25‰) [17].
\nIsotopic fingerprint of naturally occurring carbon.
The fractionation of organic carbon is mainly linked to the specific photosynthetic pathway featuring each plant. The terrestrial plants, classified as C3 and C4, can follow two different photosynthetic pathways. Both types synthesize organic matter characterized by δ13C values more negative than that of carbon dioxide (~−7‰), because during the photosynthesis, the produced organic substance accumulates the light isotope compared to the heavy one. The C3 plants, typical of temperate climates, produce the 3-phosphoglyceric acid, a compound with three carbon atoms (Calvin cycle) with an average value of δ13C of about −26.5‰. The C4 plants generate oxaloacetate, a compound with four carbon atoms (Hatch-Slack cycle) characterized by a value of δ13C around −12.5‰.
\nThe chemical composition of animal tissues is related to the food sources they assimilate, and therefore, it reflects the isotopic composition of the diet [23, 24]. The enrichment between primary producers and consumers (herbivores) has been estimated to be approximately +5‰, whereas at the successive trophic levels, the enrichment is less marked (+1‰) [25]. Thus, the isotopic value detected in the tissues of an organism can be potentially used as an indicator of its trophic position. However, since the variation of the δ13C values due to trophic passages is relatively modest, δ13C is mainly used to trace the primary carbon source used [26].
\nThrough the analysis of the stable carbon isotopes, it is also possible to differentiate terrestrial and marine trophic webs. The “marine” carbon derives from the dissolved inorganic carbon (dissolved bicarbonate) characterized by an isotopic value equal to about 0‰, while the “terrestrial” carbon derives from the atmospheric carbon dioxide which has a lower δ13C value (approximately −7‰). This difference is maintained at every trophic level both in the marine and terrestrial trophic chain (Figure 8).
\nVariations of δ13 carbon and δ15 nitrogen (‰) isotopes in different organisms of the terrestrial and marine food chain.
In 2016, Berto and collaborators carried out a preliminary study aimed at evaluating the potentials of stable isotope analysis to discriminate a wider range of plastic and bioplastic materials (including those highly used in packaging, such as shopping bags and plastic bottles for drinking water) (Table 1) to the scope of using this analytical technique for the identification of plastic debris in marine samples in future field surveys [27].
\nSample type | \nUse | \n
---|---|
Acrylonitrile butadiene styrene (ABS) | \nThermoplastic polymer; used for pipes, musical instruments, sport equipment, automobile industry, toys, and electronic component assemblies | \n
Fluorocarbon | \nPolymers characterized by high melting temperature, resistance to sunlight degradation and chemical inertness; used for industrial coatings (electronics, automotive, and food industry) | \n
High density polyethylene (HD PE) | \nThermoplastic polymer; used for beverage bottles, food storage containers, plastic bags, fuel tanks, piping systems, electrical boxes, folding furniture, sport equipment, storage sheds, and wood-plastic composites; packaging material for food use | \n
Low density polyethylene (LD PE) | \nUtilized as thin films used for coatings or plastic bag production, recipients made in injection molding (bottles, bags, and laboratory equipment), pipings, food containers, corrosion resistant surfaces, and computer components; packaging material for food use | \n
Low density polyethylene (LD PE) recycled | \nAs above | \n
Chlorosulfonated polyethylene (HYPALON) | \nIs a synthetic rubber; used in folding kayaks and inflatable boats, sport equipment (snowshoes), and roof coatings | \n
Polychloroprene (NEOPRENE) | \nThis synthetic rubber is more degradation resistant than the natural one and is used for corrosion-resistant coatings and hoses, clothing and equipment for water sports, car seats or covers, computer or tablet holders, mouse pads, and gloves | \n
Polyamide (PA) | \nPolymers used in carpets, textiles, sportswear, due to their strength and durability | \n
Polyethylene terephthalate glycol-modified (PETG) | \nThis strong and glass-like thermopolymer is employed in production of electronic devices, covers, food and medical applications, and credit cards; it is fully recyclable | \n
Polypropylene (PP) | \nAs it is chemically resistant to many acids, bases, and solvents, it is used for laboratory equipment, medical devices and textiles, but also for piping systems, plastic furniture, carpets, ropes, roofing waterproof membranes, insulation for electrical cables, bottles and storage boxes, and concrete additives | \n
Polystyrene (PS) | \nIn its solid form, it is employed for packaging, containers, bottles, disposable cutlery, dishes, and razors. Also widely used in foamed form in protective packaging | \n
Polytetrafluoroethylene (PTFE) | \nThis fluoropolymer is hydrophobic and nonreactive and displays an extremely low friction coefficient. It is used in industrial applications, wire production as insulators, carbon fiber and fiberglass composites production, a nonstick coating in cookware, and textiles (like Gore-Tex) | \n
Polyurethane (PU) | \nThermoplastic and thermosetting polymers are available; used for the production of cushions, mattresses (flexible foams), construction industry, wheels, tires, furniture, synthetic fibers, hard-plastic parts, shoes, and surface coatings | \n
Polyvinyl chloride (PVC) | \nProduction of door and window frames, siding, pipes, bottles, and credit cards (rigid form); also used in electrical cable insulation, inflatable products, leather imitation, and shower curtains (flexible form) | \n
Polyvinylidene difluoride (PVDF) | \nChemically, electrically and flame resistant resin, used for containers in chemical industry, pipes, and food containers. Also applied in electronics (transducers and insulators) and in medical and defense industries | \n
Styrene acetonitrile (SAN) | \nPolymer similar to polystyrene; used in plastic optical fibers, packaging material, bottles, and food container, as well as in computer products and battery cases | \n
Polysiloxanes (SILICONE) | \nUsed in electrical and thermal insulation, sealants, medical applications, and cooking utensils | \n
Polyethylene terephthalate (PET) | \nUsed for packaging of food and beverages, textiles (known as polyester), and thermoforming applications | \n
PET recycled | \nAs above | \n
LATEX/RUBBER | \nPlant-derived plastic polymer. The natural latex rubber is employed in the production of gloves, mattresses, balloons, and swim caps | \n
Polylactide (PLA) | \nIs a thermoplastic, plant-derived polyester. Used as a packaging material, compost bags, disposable tableware, gardening (mulch film), and medicine (implants) | \n
“BIO” bag | \nBiodegradable bags are used in food packaging and composting of food waste and to collect dog waste | \n
Cellulose | \nC3 plant used in bioplastic production | \n
Cotton | \nC3 plant used in bioplastic production. | \n
Potato | \nC3 plant used in bioplastic production. | \n
Rice | \nC3 plant used in bioplastic production | \n
Tomato | \nC3 plant used in bioplastic production | \n
Corn | \nC4 plant used in bioplastic production | \n
Sugarcane | \nC4 plant used in bioplastic production | \n
Plastic (petroleum and plant-derived polymers) and natural matrices analyzed in this study.
Furthermore, considering the lack of knowledge on possible changes in the carbon isotopic signature of plastics due to degradation processes in the marine environment, this study also investigated the variation of δ13C values of petroleum- and plant-derived polymers of packaging materials subjected to biotic and abiotic degradation. The study was carried out by using an isotope ratio mass spectrometer Delta V Advantage (Thermo Fisher Scientific, Bremen, Germany) coupled with an elemental analyzer Flash 2000 (Thermo Fisher Scientific, Bremen, Germany). The accuracy of the isotopic data was evaluated by the analysis of the certified polyethylene foil (−31.8 ± 0.2‰, IAEA-CH-7, International Atomic Energy Agency, Austria). The analytical precision of measurements was 0.2‰ for C.
\nThis chapter gives a review of the main insights obtained and critically discusses the potentials of the carbon isotope ratio analysis to study the behavior and fate of plastics in the aquatic environment.
\nδ13C values recorded in this study for the most used petroleum-derived plastic polymers, plant-derived polymers, some commercial items made by petroleum- and natural-derived polymers, which are largely found in the marine litter worldwide (i.e., food packaging items), and natural matrices are reported in Figure 9.
\nδ13C values determined in various petroleum- and plant-derived polymers, as well as in natural matrices analyzed in this study.
Due to their high stability and durability [28], in the last decades, petroleum-derived plastic materials have largely replaced paper and other cellulose-based products with a continuously increasing trend. At the moment, a wide variety of petroleum-based synthetic polymers are produced worldwide (approximately a total of 335 million tons in 2016), and significant quantities of these polymers end up into natural ecosystems as waste products [1].
\nThe δ13C values of the majority of the analyzed petroleum-derived plastic polymers ranged over a wide interval, that is, between −33.97 and –25.41‰. Only a few polymers, such as PTFE, silicon, and ABS showed more negative δ13C values (−40.70 ± 1.17, −39.37 ± 0.27, and − 35.17 ± 0.98‰, respectively), possibly due to fractionation processes during their synthesis.
\nWith the exclusion of PTFE, ABS, and silicon, the recorded δ13C range results are comparable to that reported for crude petroleum [29]. Petroleum is constituted by a complex mixture of organic substances, with a predominance of hydrocarbons, whose exact composition depends on the site of extraction. Petroleum usually shows negative values of δ13C, ranging between −34 and −18‰ depending on the specific extraction field. In fact, as reported by Stahl [29], petroleum could be originated from the lipid fraction of organic matter. In particular, the carbon isotopic value of petroleum can vary in relation to the marine vs. terrestrial origin of the source, with an enrichment of 12C with respect to 13C in the marine environment compared to the terrestrial one [30].
\nInterestingly, different δ13C values were recorded for some polymers as pure material and once in packaging commercial items. For instance, a significant (p < 0.05) more negative δ13C value was determined in the HDPE shopping bag for food use with respect to the original HDPE polymer. This could be related to the addition of some organic additives (i.e., stabilizers) in the final materials used for food packaging. In fact, depending on the commercial use, plastic formulations can be enriched with monomeric ingredients to improve their processing, end-use performance, and appearance (e.g., colorants, photostabilizers, etc.). Among these possible additives, our preliminary data excluded colorants as the main cause of isotopic variation in the investigated samples. These results were confirmed by the lack of significant difference among polymers of different colors (p > 0.001). The independence of the δ13C value from the plastic color could provide an important analytical advantage to the isotopic approach over some of the other analytical methods used for plastic characterization. In particular, the spectroscopic methods have been proved to be limited by the color of the plastic samples, because of the occurrence of interferences due to a decrease of the diffuse reflection intensity in dark color samples [31]. Further investigation and larger analytical data set are required in order to strength these results.
\nTo reduce the impact of plastic debris in the environment, recyclable and more biodegradable polymers (i.e., plant-derived polymers) have been introduced increasingly into the market [10]. Plant-derived plastic polymers used for food packaging, such as bags and bottles for drinking water, showed a significant difference in isotopic values with respect to the petroleum-derived plastic products. In fact, petroleum-derived packaging materials for food use, such as shopping bags for fruits and vegetables (HD PE) and plastic bottles for drinking water (PET), were characterized by the δ13C mean values of −33.97 ± 1.15 and − 27.84 ± 1.71‰, respectively, whereas plant-derived supermarket envelopes (“BIO” bags) and bottles (PLA, a biodegradable polyester derived from the fermentation of starch and condensation of lactic acid) recorded the δ13C mean values of −25.30 ± 0.70 and −13.87 ± 2.18‰, respectively. As regards to the results obtained for “BIO” bags, values reflected those of C3 plants, while for PLA, the analyses highlighted δ13C values similar to those of C4 plants, suggesting their specific origin.
\nThis difference suggests that stable isotope analysis could be a useful method to discriminate between petroleum-and plant-derived plastic debris [21, 27]. The most used biopolymers are in fact produced starting from C3 (rice, potatoes, cotton, and cellulose) and C4 (corn and sugarcane) plants, species which differ for photosynthetic pathways and, consequently, for the carbon fingerprint. C3 plants recorded more negative δ13C values (ranging from −30 to −25‰) than C4 plants (ranging from −13 to −11‰), in agreement with Suzuki et al. and authors therein [21]. Considering the isotopic signature of the “BIO” bags, a common and widespread biodegradable product used for many commercial purposes, δ13C values are generally comparable with those reported for C3 plants. Regarding “recycled” polymers, LD PE recycled envelopes showed a δ13C mean value of −27.75‰. The presence of a low quantity of other polymers as impurities or different recycle processes could explain the less negative average value with respect to the row LD PE (−30.19‰) given by an 13C enrichment or depletion (fractionation).
\nThe influence of natural degradation processes on the fractionation of carbon in plastic materials under marine conditions, according to a preliminary field study carried out by Berto et al. [27] in Venice lagoon, is showed in Figure 10. Over a 60-day period and under variable conditions of temperature and salinity (i.e., 24–35°C and 7.8–8.1, respectively), the δ13C values of both “BIO” bags and HD PE bags showed a gradual decrease toward less negative values, recording a δ13C variation (Δδ13C) of 1.15 and 1.78‰, respectively. This shift could be reasonable due to physical, chemical, and/or biological degradation, even if the latter is a controversial matter.
\nDegradation of “BIO” bag and HD PE bag in lagoon environment, reflected by δ13C variation in time.
The degradation of plastic polymers in the environment involves many factors (photodegradation, thermooxidation, hydrolysis, and biodegradation by microorganisms) [32], and it proceeds according to the rates highly dependent on the environmental conditions. For instance, several authors have reported that degradation processes and the rate of hydrolysis of most plastic polymers become insignificant in the ocean when the temperature and the concentration of oxygen are reduced [32, 33].
\nHowever, the physical/mechanical degradation occurring in the marine environment can alter the plastic polymers at the surface layer and favor the starting of microbial deterioration processes. By considering that, in many biochemical reactions, such as autotrophic fixation of CO2 by plants [34] and microbial degradation processes, the lightest isotope (12C) are preferentially used as a substrate over the heaviest isotopes, and the different isotopic values recorded by Berto et al. [27] for “pristine” and “aged” plastic materials sampled from the marine environment suggested the occurrence of degradation processes. Further studies are needed to evaluate the pathway and the time featuring this process.
\nIn fact, some researchers are confident in thinking that biopolymer (such as cellulose in plants) plastics are not generally biodegradable. Bacteria and fungi coevolved with natural materials, while plastics have only been around for about 70 years. So microorganisms simply have not had much time to evolve the necessary biochemical tool kit to latch onto the plastic fibers, break them up into the constituent parts, and then use the resulting chemicals as a source of energy and carbon that they need to grow [35]. However, in 2016 a team of researchers from Kyoto Institute of Technology and Keio University, after collecting environmental samples containing PET debris, observed a novel bacterium (Ideonella sakaiensis 201-F6) which is able to use PET plastic for carbon growth. This bacterium produces two distinct enzymes hydrolizing PET plastics into terephthalic acid and ethylene glycol. This discovery has potential importance for the recycling process of PET [36].
\nA large number of tests (respirometric, loss of weight, tensile strength, spectroscopic) have been conducted to evaluate the extent of degradation of polymers, either alone or in blended forms, mainly under terrestrial environmental conditions.
\nIt is worth noting that most recalcitrant polymers can be degraded to some extent in the appropriate environment at the right concentration. A screening program to study the ability of organisms and enzymes in degrading plastic polymers in a marine environment is required, considering the increasing importance of biodegradable plastics in the last few years.
\nConsidering the new data presented in this study, it is possible to hypothesize the new paths for stable isotope research applied to the plastic polymers in the environment.
\nIn this chapter, we focused on plastic polymers, both petroleum- and plant-derived, commonly used in commercial packaging products for food use, giving preliminary overview of their δ13C values. The low difference of δ13C values among polymers suggested that the different chemical pathways used for their synthesis did not induce fractionation of carbon stable isotopes, yielding to δ13C values meaningful of the row material (i.e., petroleum and terrestrial plants). Thus, this technique showed interesting perspective for its application in discriminating petroleum- and plant-derived polymers in marine samples.
\nFurthermore, the method showed to be unaffected by additional variables, such as color, and thus, it seems a valuable alternative to the spectroscopy methods for the characterization of plastic polymers in marine samples, which in contrast found the analytical limitation especially with dark colored plastic samples.
\nFinally, an important potential of the isotope mass spectrometry is its application to the study of the degradation processes (abiotic and biotic) of plastic waste released in the marine environment and the assessment of the degradation rates. In particular, this technique could be applied for analysis of suspended plastic debris, after filtration of both marine and fresh water samples collected along the water column. In this regard, however, further studies are needed to discriminate the isotopic values of suspended organic matter from those of plastic polymers, with major concern for micro and nanoplastics. Such possible application is of particular interest for the estimation of the fate of plastics in the marine environment and the evaluation of the effectiveness of the policies developed to reduce the environmental impact of marine litter.
\nThe authors are grateful to Davide Zanella for graphical support and to Guido Giazzi and Luca Simonotti of Thermo Fischer Scientific for analytical support.
\nNo potential conflict of interest was reported by the authors.
Among the available biomaterials, hydrogels, three-dimensional polymeric networks capable of imbibing large amounts of water or biological fluids, have proved their value in diverse biomedical applications [1, 2, 3]. In addition to the swelling property of the hydrogels, their biocompatibility, good mechanical properties, tunable chemical structure, and three-dimensional physical structure have made them one of the promising class of materials for tissue engineering [4, 5], pharmaceutical applications [6, 7], and biomaterials science [8]. In recent years, with the advancements in technology, interest in microscopic (microgels) and nanoscopic hydrogels (nanogels) has increased [9, 10].
\nMicrogels, hydrogel particles formed by physical or chemical cross-linking of polymer networks in microscale size [11], have exceptional properties like large surface area, tunable size from micrometers to nanometers, ease in synthesis, control over particle size, responsiveness to environmental factors, and an interior network for the incorporation of therapeutic agents [12, 13].
\nStimuli-responsive properties can be incorporated into gels. Microgels may respond to a number of stimuli like pH, ionic strength, specific ions, external fields, and temperature [14, 15, 16, 17]. Such DDSs are designed whether to target tissues, to reach specific intracellular locations, or to promote drug release [18]. Brief overview of the types of stimuli-responsive microgels is given below.
\nSeveral classes of polymers, including poly(N-isopropylacrylamide) and poly(ethylene glycol), demonstrate swelling/deswelling changes in response to temperature [19, 20]. With increase in temperature, these systems have reduced solvency and pronounced deswelling. Nolan et al. [21] demonstrated higher insulin release from poly (N-isopropyl acrylamide), with increasing temperature. Temperature-dependent aggregation property of such thermosensitive microgel systems may also be utilized in drug delivery, e.g., at elevated temperature; due to aggregation of PNIPAM microgels particle inside the cancerous cell, toxicity was observed [22].
\nMicrogels can be designed to be triggered by the concentration of particular compounds, like insulin [23, 24]. For example, insulin containing poly (diethyl aminoethyl methacrylate) microgels conjugated with glucose oxidase [25]. The enzymatic conversion of glucose to gluconic acid causes pH-responsive swelling of the polymer network leading to release of insulin. In another study Sui et al. [26] reported trifluoperazine triggered volume transition in calmodulin-based hydrogels.
\nMicrogel systems may also respond to external fields (ultrasound, light, and magnetic fields). Patnaik et al. [27] investigated photoresponsive drug release in azo-dextran nanogels based on (trans-cis) photoisomerization of an azobenzene present in the cross-linker. For this system, the release of drug was slower for trans-configuration while faster for cis-configuration.
\nMetal nanoparticles may be used for optical or magnetic heating. When temperature-responsive microgels are combined with metals, heat induced by the external fields may result in deswelling, leading to release of the absorbed drugs. Using this perspective, Wong et al. [28] explored Fe-containing PNIPAM microgels. The microgels showed ability to manifest local heating attributed to an oscillating magnetic field. With increasing temperature microgels deswelled. Similar kind of triggering was also manifested in other studies, where light-originated heating of absorbed metal nanoparticles was used to induce local heat, provoking permeability variations in temperature-responsive polymers [29, 30, 31].
\nMicrogel degradation in response to stimuli offers another way of controlled drug delivery [32, 33]. Such systems are commonly based on biodegradable microgels, occasionally surrounded by a shell impermeable to the drug. In later case, microgel degradation causes increased osmotic pressure, finally breaking the shell and drug release. Examples include dextran microgels coated by different polyelectrolyte multilayer systems [34] and lipid-coated microgels for the release of doxorubicin [35].
\nBiodegradable acrylamide/bisacrylamide microgels containing acetal linkers were investigated by Murthy et al. [36]. Biodegradation stimulated by low pH, resulting from acid-catalyzed hydrolysis of acetal linkage, was responsible for drug release. Similarly, Bromberg et al. [37] investigated poly (acrylic acid)-containing microgels cross-linked with disulfide groups. The chemical reduction of the disulfide bonds manifested the swelling of these systems.
\npH-responsive microgels represent one of the major approaches for microgel-based delivery of biomacromolecular drugs. Of the many stimuli, alteration in pH is markedly fascinating because of the availability of pH gradients admissible for drug targeting. For example, pH gradients between normal tissues and some pathological sites, between the extracellular environment and some cellular compartments, and along the gastrointestinal (GI) tract are well characterized [38]. Orally administered drug encounters a pH gradient as it move from the stomach (pH 1–2, fasted state) to the duodenum (pH of about 6) and along the jejunum and ileum (pH 6–7.5) [39, 40]; therefore, attempts to avoid deterioration of drug and/or to promote intestinal absorption by exploiting this pH gradient is promising. pH-responsive polymeric networks, hence, have been extensively studied for the design of efficient carriers for drug delivery [41].
\npH-responsive polymers are generally fabricated by inserting pendant acidic or basic functional groups to the backbone of the polymer. These functional groups either accept or release protons in response to appropriate pH and changes in the ionic strength of the surrounding aqueous media [42]. Polymers with acidic groups are unexpanded at low pH values, since the acidic groups are protonated and unionized. While increasing pH acidic groups are ionized, the resulting negatively charged polymer expands. The opposite behavior will be observed in the case of polybasic polymers [43, 44]. These systems can form polyelectrolytes with water, and microgels fabricated from weak polyelectrolytes demonstrate a pH-responsive volume phase changes. On the basis of the framework of polyelectrolyte, pH-responsive microgels can be classified as cationic, basic, or amphoteric. For instance, poly(acrylic acid) and polyethylenimine are weak polyacid and a polybase, respectively.
\nMethods used for the synthesis of microgels can be divided into two major ideas:
The synthesis of microgels in homogeneous phase
The synthesis of microgels in heterophase
The first approach is based on the investigations of Staudinger [45], who prepared inter- and intramolecularly cross-linked microgels by free radical cross-linking copolymerization of monomers in dilute solutions. However, the resulting internal structure of microgels was not well established, but investigations performed on these systems were key step to understand the process of gel formation [46].
\nOther techniques include coacervation and desolvation. In both techniques phase separation of readily formed polymers takes place, resulting in micro-/nanoparticles which are then cross-linked. Figure 1 represents typical steps involved in coacervation method. Phase separation is usually induced by changing temperature, adding salt, nonsolvent addition, non-compatible polymer addition, or polymer-polymer interaction. The resulting coacervate (polymer droplet) is then solidified and stabilized forming microgel particle. This technique is usually employed in synthesis of microgels from biopolymers such as (modified) gelatin or chitosan. For example, pH-responsive chitosan nanoparticles were synthesized by complex coacervation [47] and two-step desolvation route was involved in synthesis of gelatin nanoparticles [48].
\nSchematic presentation of coacervation technique.
Heterophase copolymerization of monomers with cross-linking agents in aqueous solution can be distinguished as:
Dispersion/precipitation polymerization
Miniemulsion polymerization
Microemulsion polymerization
In this technique, polymerization generally starts in a homogenous solution of monomers and cross-linkers [49, 50]; as polymerization progresses, the monomer and the developed oligomers remain soluble; after achieving the critical length phase, separation takes place by enthalpic precipitation leading to particle nuclei formation. The nuclei aggregate to form large particles that carry on growing resulting into microgel formation. In dispersion polymerization stabilizers can be added to regulate the particle size and to keep particles in narrow size distribution [51]. The described method is schematically presented in Figure 2.
\nPrecipitation polymerization (a) initiation of polymerization and chain growth, (b) precipitation and nuclei formation, (c) particle growth, and (d) microgels.
Dispersion polymerization technique was employed for the synthesis of pH-sensitive poly((2-dimethylamino)ethyl methacrylate) microgels with diameter of about 100–200 nm in dry sate [52]. The microgels exhibited volume phase change at about pH 8, with 32 times decrease in diameter. Dispersion polymerization was involved in the preparation of hydrophilic microparticles of poly(2-hydroxyethyl methacrylate) [53].
\nDuracher et al. [54] synthesized thermoresponsive microgels by precipitation polymerization of N-isopropylmethacrylamide. The prepared microgels were found to be temperature sensitive. Moreover, with the modifications in the synthetic protocol, more complex microgel structures can be synthesized. Examples include temperature- and pH-sensitive microgels prepared by copolymerization of N-isopropylmethacrylamide with acrylic acid [55], vinyl acetic acid [56, 57], or 2-aminoethyl methacrylate hydrochloride [58].
\nOne approach to synthesize complex structures, e.g., core-shell microgels or hollow microgels, involves polymerization of different monomers and/or already formed seed particle. Core-shell microgels have structurally separated zones of different polymers. Zhou et al. [59] synthesized temperature sensitive microgels based on oligo(ethylene glycol). The microgels were stable across the important physiological temperature range with adjustable volume phase changes.
\nIn general, microemulsions can be prepared as direct oil-in-water (O/W) or inverse water-in-oil (W/O) emulsions. The inverse emulsions are widely investigated for the formulation of hydrogel nanoparticles. In this approach, dispersed phase consists of either monomer having ability to polymerize or prepolymers with ability of cross-linking dissolved in water is added to a continuous phase of organic medium having large amount of oil-soluble surfactant. The mixture is stirred to achieve thermodynamically stable microemulsion. Synthesis of microgels takes place inside the droplets, e.g., via free radical polymerization. Initiation of polymerization takes place either from the interior of droplets or from the continuous phase [60]. Figure 3 illustrates the microgel synthesis in W/O emulsion.
\nIllustration of microgel preparation via inverse emulsion polymerization.
Shen et al. [61] synthesized poly(acrylamide-co-acrylic acid) microgels by polymerization in inverse microemulsion. The effect of chemical constitution on size, morphology, swelling behavior, thermal properties, and pH-sensitivity was explored. The size of p(AM-co-AA) microgels was larger in comparison to PAM microgels. The microgels exhibited pH-responsive behavior and have higher swelling ratio, with an increase in acrylic acid content.
\nIn another study, microemulsion polymerization phenomenon was employed for the copolymerization of methacrylic acid and 2-ethylhexyl acrylate to demonstrate colon-specific delivery of drug. An anticancer drug (5-fluorouracil) was entrapped inside the copolymer through solvent evaporation method. In vitro drug release studies performed at different pH levels revealed pH-dependent release of 5-fluorouracil in a sustained manner [62].
\nMiniemulsions in general are kinetically stable emulsions; considerably less surfactant is required for the droplet stabilization [63]. This approach is versatile and allows utilization of different monomers, functional compounds incorporation, and the accurate adaptation of droplets and particles size [64, 65]. In general, high deformation forces are applied to pre-emulsion of droplet leading to uniform distribution of well-defined nanodroplets (50–500 nm). The surfactant present in the system obstructs the coalescence of these nanodroplets; in addition, the costablizer added to dispersed phase prevents Ostwald ripening leading to kinetically stable miniemulsion [66].
\nMiniemulsions can be classified as direct (oil-in-water) or inverse (water-in-oil) systems. Oil-in-water miniemulsification is a well-established approach for the polymerization of hydrophobic monomers for the formulation of polymeric latexes [63]; on the other hand, the inverse method involves diverse synthetic pathways for the formation of nanohydrogels [67]. One approach involves the free radical copolymerization of hydrophilic monomers with cross-linking agents in dispersed droplets of either aqueous solutions of these compounds or their mixture without additional solvent. The monomers must be immiscible with the continuous phase. Examples include the formation of polyacrylamide (PAAm)- [68] and PHEMA-based [65] microgels. Figure 4 schematically represents the described synthetic pathway.
\nSchematic illustration of radical cross-linking in inverse miniemulsion.
Another approach is cross-linking of preformed polymers in inverse miniemulsion. In this method mixture of two W/O emulsions (A and B) are ultrasonicated. Emulsion A constitutes the solution of already formed polymer, and emulsion B constitutes solution of cross-linker. Ultrasonication leads to mixing of the components of both emulsions, inducing the cross-linking reaction. This method has been employed for the synthesis of covalently cross-linked gelatin microgels [69]. In another study, temperature-responsive nanogels poly(N-isopropylacrylamide) nanogels were fabricated by nanoemulsion polymerization as smart delivery systems [70].
\npH-responsive microgels have demonstrated a number of medical applications (Table 1). Few examples from the literature are demonstrated here.
\nPolymers | \nPolymeric DDSs | \nDrug | \nApplication | \nReference | \n
---|---|---|---|---|
GG-g-PDMAEMA | \nIPN-Microgels | \n5 fluorouracil | \nAntitumor activity | \n[72] | \n
OPF-SMA microgels | \nMicrogels | \nDoxorubicin | \nAntitumor activity | \n[73] | \n
MEMA-co-IA | \nMicrogels | \nEsomeprazole | \nIntestinal delivery | \n[76] | \n
P(MMA-g-EG) | \nMicrogels | \nInsulin | \nOral peptide delivery | \n[82] | \n
P(AM)-g-carrageenan and sodium alginate | \nHydrogel beads | \nKetoprofen | \nFor colon-targeted delivery | \n[83] | \n
Methacrylate derivatives of dextran and concanavalin | \nMicrogels | \nInsulin | \nSelf-regulated insulin delivery | \n[84] | \n
Alg and chemically modified carboxymethyl CS | \nMicrogels | \nProtein drug | \nFor oral delivery | \n[85] | \n
Examples of various applications of microgels as drug delivery carriers.
pH-responsive p(NIPAAm/AA) microgels were fabricated for transferrin-based targeting of cancer [71]. These microgels were able for specific delivery to human cervical carcinoma cell line (HeLa) cells. In another study methacrylic-based copolymeric pH-sensitive nanogels were prepared for targeted delivery of 5-fluorouracil to the colon [62]. Recently, Eswaramma et al. [72] developed pH-sensitive interpenetrating polymer network (IPN) microgels of chitosan and guar gum-g-poly((2-dimethylamino)ethyl methacrylate) (GG-g-PDMAEMA) and treated as responsive drug carriers for an anticancer agent, 5-fluorouracil (5-FU). The microgels showed encapsulation efficiency up to 81%, and the release kinetics showed pH-dependent drug release with an excellent controlled release pattern for 5-FU over a period of more than 24 h.
\nDadsetan et al. [73] used a copolymer of oligo(poly(ethylene glycol) fumarate) (OPF) and sodium methacrylate (SMA) to fabricate the pH-responsive microgels for the delivery of doxorubicin (DOX) in order to optimize its antitumor activity while minimizing its systemic toxicity. The resulting microgels exhibited sensitivity to the pH and ionic strength of the surrounding environment and demonstrated that DOX was efficiently loaded into the microgels and released in a controlled fashion via an ion exchange mechanism. The antitumor activity of the released DOX was assessed using a human chordoma cell line revealed that OPF-SMA microgels prolonged the cell-killing effect of DOX.
\nTripahi et al. [74] developed a pH-sensitive intragastric floating polymer microgel beads containing clarithromycin for the treatment of peptic ulcer. The optimized formulation successfully maintained minimum inhibition concentration of clarithromycin at the infection site and potentially allowed penetration of the drug inside the mucus gel. Varma et al. [75] have chemically modified guar gum (GG) as a pH-sensitive copolymer and formulated intestinal-targeting esomeprazole magnesium (ESO) nanoparticles (NPs). Polyacrylamide-grafted guar gum copolymer was synthesized by free radical polymerization, and ESO-loaded pH-sensitive NPs were prepared by nanoemulsification polymer cross-linking method. In vitro release studies showed pH-dependent drug release. The pH-sensitive NPs resisted drug release in acidic pH and delayed the release in alkaline environment.
\nIn another study novel pH-responsive poly(methoxyethyl metacrylate-co-itaconic acid) microgels were fabricated and evaluated for controlled and extended delivery of model acid labile drug (esomeprazole). The designed microgels successfully protected the drug from acidic environment of the stomach, with potential intestinal drug delivery over an extended period of time. Thus, suggesting p(MEMA-co-IA) micro-hydrogels as good candidate of an orally administrated site-specific and controlled drug delivery system, such as proton-pump inhibitors, proteins, and peptides [76]. In similar studies p(hydroxyethyl methacrylate-co-itaconic acid) microgels, poly(2-ethyl hexyl acrylate-co-IA) microgels, and poly(butyl acrylate-co-itaconic acid) microgels showed pH-responsive swelling and drug release behavior with maximum release at pH 7.4 and negligible release at pH 1.2 suggesting the potential use of these drug delivery system for oral intestinal delivery of therapeutics [77, 78, 79].
\nA novel 5-aminosalicylic acid (5-ASA)-loaded pH-sensitive poly(methoxy ethylene glycol-caprolactone-co-methacrylic acid-co-poly(ethylene glycol) dimethacrylate) microgels were prepared for treatment of ulcerative colitis. The microgels were found to be shrunk at pH 1.2 and expanded at pH 7.4. Safety evaluation of microgels was conducted by maximum tolerated dose (MTD) method. The 5-ASA/microgels were used to treat ulcerative colitis in mice, and free 5-ASA was used as positive control. It was found that 5-ASA has good efficacy for treating ulcerative colitis, and microgels entrapping 5-ASA could significantly enhance the colon targeting to improve its efficacy [80].
\nXua et al. [81] fabricated novel biodegradable and pH-sensitive microgels based on poly(ε-caprolactone)-pluronic-poly(ε-caprolactone)-dimethacrylate, methyl acrylic acid, and poly(ethylene glycol)dimethacrylate cross-linked with N,N′-methylenebisacrylamide. Hydrophilic model drug (vitamin B12) was loaded to investigate in vitro release profile; the developed drug delivery system demonstrated pH-sensitive drug release behavior.
\nLowman et al. [82] studied the use of poly(methacrylic-g-ethylene glycol) (P(MMA-g-EG)), a hydrogel microparticle that responds to a change in pH for the transport of orally administered insulin. This drug is a peptide labile to proteolytic degradation in the acidic stomach. Thus this pH-responsive carrier protected insulin in the acidic environment of the stomach as a result of the intermolecular interaction that prevented the hydrogel from swelling. But once the microparticles reached alkaline and neutral environments, namely, the intestine, the interaction that occurred previously was lost, and the pore size of the hydrogel increased, thus allowing insulin release.
\nThis chapter has attempted the compilation of the advances in the field of stimuli-responsive microgel technology and their application in controlled release drug delivery carriers. The ultimate goal for controlled drug release is to maximize therapeutic activity while minimizing the negative side effects of the drug. In this regard, versatile micro- and nanoscale delivery approaches based on smart polymers have already been established to seek the distinct advantages in drug delivery. However, the new polymers and nanocarriers definitely require extensive consideration of toxicological and immunological issues, which are often ignored during the research phase.
\nThere is no conflict of interest.
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\n\n*INTECHOPEN LIMITED is a privately owned company registered in England and Wales, No. 11086078 Registered Office: 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK
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