Chitosan and Its Derivatives - Biomaterials with Diverse Biological Activity for Manifold Applications

Author(s): Paulina Paul, Beata Kolesinska*, Witold Sujka.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 9 , 2019

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Graphical Abstract:


Derived from chitin, chitosan is a natural polycationic linear polysaccharide being the second most abundant polymer next to cellulose. The main obstacle in the wide use of chitosan is its almost complete lack of solubility in water and alkaline solutions. To break this obstacle, the structure of chitosan is subjected to modification, improving its physic-chemical properties and facilitating application as components of composites or hydrogels. Derivatives of chitosan are biomaterials useful for different purposes because of their lack of toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the methods of chemical modifications of chitosan which allow to obtain tailor- made properties required for a variety of biomedical applications. Selected pharmaceutical and biomedical applications of chitosan derivatives are also highlighted. Possibility to manage waste from arthropod and crab processing is also emphasized.

Keywords: Chitin, chitosan, chitosan modification, wound dressing, wound healing, antibacterial activity, pharmaceutical applications, biomedical applications.

Du, Y.; Zhao, Y.; Dai, S.; Yang, B. Preparation of water-soluble chitosan from shrimp shell and its antibacterial activity. Innov. Food Sci. Emerg. Technol., 2009, 10(1), 103-107.
Mucha, M. Chitozan: wszechstronny polimer ze źródeł odnawialnych (Chitosan: a versatile polymer from renewable sources); WNT: Warsaw, 2010.
Pillai, C.K.S.; Paul, W.; Sharma, C.P. Chitin and chitosan polymers: Chemistry, solubility and fiber formation. Prog. Polym. Sci., 2009, 34(7), 641-678.
Pusateri, A.E.; McCarthy, S.J.; Gregory, K.W.; Harris, R.A.; Cardenas, L.; McManus, A.T.; Goodwin, Jr, C.W. Effect of a chitosan-based hemostatic dressing on blood loss and survival in a model of severe venous hemorrhage and hepatic injury in swine. J. Trauma Acute Care Surg., 2009, 54(1), 177-182.
No, H.K.; Meyers, S.P.; Lee, K.S. Isolation and characterization of chitin from crawfish shell waste. J. Agric. Food Chem., 1989, 37(3), 575-579.
Struszczyk, H. Chitin and Chitosan, Part I. Properties and Production. Polimery, 2002, 47(5), 316-325.
Gagne, N.; Simpson, B.K. Use of proteolytic enzymes to facilitate the recovery of chitin from shrimp wastes. Food Biotechnol., 1993, 7(3), 253-263.
Gildberg, A.; Stenberg, E. A new process for advanced utilisation of shrimp waste. Process Biochem., 2001, 36(8-9), 809-812.
Tsigos, I.; Martinou, A.; Kafetzopoulos, D.; Bouriotis, V. Chitin deacetylases: New, versatile tools in biotechnology. Trends Biotechnol., 2000, 18(7), 305-312.
Jayakumar, R.; Prabaharan, M.; Kumar, P.S.; Nair, S.V.; Tamura, H. Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol. Adv., 2011, 29(3), 322-337.
Olteanu, C.E. Applications of functionalized chitosan. SCSCC6,, 2007, 8(3), 227-256.
Rinaudo, M. Chitin and chitosan: Properties and applications. Prog. Polym. Sci., 2006, 31(7), 603-632.
Chakrabarty, T.; Kumar, M.; Shahi, V.K. Chitosan based membranes for separation, pervaporation and fuel cell applications: Recent developments. Biopolymers, 2010, 10, 201-226.
Kim, S.K., Ed.; Chitin, chitosan, oligosaccharides and their derivatives: biological activities and applications; CRC Press, 2010.
Zielinska, D.; Struszczyk, M.H.; Madej-Kiełbik, L.; Chmal-Fudali, E.; Kucharska, M.; Wisniewska-Wrona, M.; Brzoza-Malczewska, K. Design of new-generation usable forms of topical haemostatic agents containing chitosan. Molecules, 2017, 22(12), 2240.
Mironov, A.V.; Vikhoreva, G.A.; Kil’deeva, N.R.; Uspenskii, S.A. Reasons for unstable viscous properties of chitosan solutions in acetic acid. Polym. Sci. Ser. B, 2007, 49(1-2), 15-17.
Szymańska, E.; Winnicka, K. Stability of chitosan-a challenge for pharmaceutical and biomedical applications. Mar. Drugs, 2015, 13(4), 1819-1846.
Furuike, T.; Komoto, D.; Hashimoto, H.; Tamura, H. Preparation of chitosan hydrogel and its solubility in organic acids. Int. J. Biol. Macromol., 2017, 104, 1620-1625.
Khanmohammadi, M.; Elmizadeh, H.; Ghasemi, K. Investigation of size and morphology of chitosan nanoparticles used in drug delivery system employing chemometric technique. Iran. J. Pharm. Res., 2015, 14(3), 665-675.
Ostrowska-Czubenko, J.; Pieróg, M.; Gierszewska, M. Modification of Chitosan – a Concise Overview. Wiadomości Chemiczne, 2016, 70(9-10), 657-679.
d’Ayala, G.G.; Malinconico, M.; Laurienzo, P. Marine derived polysaccharides for biomedical applications: Chemical modification approaches. Molecules, 2008, 13(9), 2069-2106.
Kurita, K. Controlled functionalization of the polysaccharide chitin. Prog. Polym. Sci., 2001, 26(9), 1921-1971.
Sashiwa, H.; Aiba, S.I. Chemically modified chitin and chitosan as biomaterials. Prog. Polym. Sci., 2004, 29(9), 887-908.
Kurita, K. Chitin and chitosan: Functional biopolymers from marine crustaceans. Mar. Biotechnol., 2006, 8(3), 203-226.
Mourya, V.K.; Inamdar, N.N. Chitosan-modifications and applications: opportunities galore. React. Funct. Polym., 2008, 68(6), 1013-1051.
Prashanth, K.H.; Tharanathan, R.N. Chitin/chitosan: Modifications and their unlimited application potential—an overview. Trends Food Sci. Technol., 2007, 18(3), 117-131.
Kalia, S.; Avérous, L. (Eds.) Biopolymers: Biomedical and Environmental Applications, John Wiley & Sons, Inc. Hoboken, New Jersey, and Scrivener Publishing LLC, Salem, Massachusetts, 2006.
Yao, K.; Li, J.; Yao, F.; Yin, Y. (Eds.) Chitosan-based hydrogels: functions and applications, CRC Press, 2011.
Ji, J.; Wang, L.; Yu, H.; Chen, Y.; Zhao, Y.; Zhang, H.; Saleem, M. Chemical modifications of chitosan and its applications. Polym. Plast. Technol. Eng., 2014, 53(14), 1494-1505.
Chopin, N.; Guillory, X.; Weiss, P.; Bideau, J.L.; Colliec-Jouault, S. Design polysaccharides of marine origin: Chemical modifications to reach advanced versatile compounds. Curr. Org. Chem., 2014, 18(7), 867-895.
Sarmento, B. das Neves, J. (Eds.) Chitosan-based systems for biopharmaceuticals: delivery, targeting and polymer therapeutics, John Wiley & Sons Inc. 2012.
Dufresne, A.; Sabu, T.; Pothan, L.A., Eds.; Biopolymer Nanocomposites: Processing, Properties, and Applications; John Wiley & Sons, Inc., 2013.
Jain, A.; Gulbake, A.; Shilpi, S.; Jain, A.; Hurkat, P.; Jain, S.K. A new horizon in modifications of chitosan: Syntheses and applications. Crit. Rev. Ther. Drug Carrier Syst., 2013, 30(2), 91-181.
Muzzarelli, R.A.A.; Muzzarelli, C. Chitosan chemistry: Relevance to the biomedical sciences.In Polysaccharides I. Structure, Characterisation and Use; Heinze, T., Ed.; Springer, 2005, pp. 151-209.
Alves, N.M.; Mano, J.F. Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications. Int. J. Biol. Macromol., 2008, 43(5), 401-414.
Prabaharan, M. Chitosan derivatives as promising materials for controlled drug delivery. J. Biomater. Appl., 2008, 23(1), 5-36.
Badawy, M.E.; Rabea, E.I. A biopolymer chitosan and its derivatives as promising antimicrobial agents against plant pathogens and their applications in crop protection. Int. J. Carbohydr. Chem. IJCC, 2011.
Giri, T.K.; Thakur, A.; Alexander, A.; Badwaik, H.; Tripathi, D.K. Modified chitosan hydrogels as drug delivery and tissue engineering systems: Present status and applications. Acta Pharm. Sin. B, 2012, 2(5), 439-449.
Yong, S.K.; Shrivastava, M.; Srivastava, P.; Kunhikrishnan, A.; Bolan, N. Environmental applications of chitosan and its derivatives. Rev. Environ. Contam. Toxicol., 2015, 233, 1-43.
Ma, J.; Sahai, Y. Chitosan biopolymer for fuel cell applications. Carbohydr. Polym., 2013, 92(2), 955-975.
Shukla, S.K.; Mishra, A.K.; Arotiba, O.A.; Mamba, B.B. Chitosan-based nanomaterials: A state-of-the-art review. Int. J. Biol. Macromol., 2013, 59, 46-58.
Kyzas, G.Z.; Bikiaris, D.N. Recent modifications of chitosan for adsorption applications: A critical and systematic review. Mar. Drugs, 2015, 13(1), 312-337.
Wang, J.; Chen, C. Chitosan-based biosorbents: Modification and application for biosorption of heavy metals and radionuclides. Bioresour. Technol., 2014, 160, 129-141.
Vakili, M.; Rafatullah, M.; Salamatinia, B.; Abdullah, A.Z.; Ibrahim, M.H.; Tan, K.B.; Amouzgar, P. Application of chitosan and its derivatives as adsorbents for dye removal from water and wastewater: A review. Carbohydr. Polym., 2014, 113, 115-130.
Macquarrie, D.J.; Hardy, J.J. Applications of functionalized chitosan in catalysis. Ind. Eng. Chem. Res., 2005, 44(23), 8499-8520.
Ahmed, S.; Ikram, S. Chitosan and its derivatives: A review in recent innovations. Int. J. Pharm. Sci. Res., 2015, 6(1), 14-30.
Sahoo, D.; Nayak, P.L. Chitosan: The most valuable derivative of chitin In:. Biopolymers: Biomedical and Environmental Applications, Susheel Kalia, Luc Avérous, Ed. Scrivener Publishing LLC, 2011, pp. 129-166
Aranaz, I.; Harris, R.; Heras, A. Chitosan amphiphilic derivatives. Chemistry and applications. Curr. Org. Chem., 2010, 14(3), 308-330.
Jayakumar, R.; Nwe, N.; Tokura, S.; Tamura, H. Sulfated chitin and chitosan as novel biomaterials. Int. J. Biol. Macromol., 2007, 40(3), 175-181.
Jayakumar, R.; Selvamurugan, N.; Nair, S.V.; Tokura, S.; Tamura, H. Preparative methods of phosphorylated chitin and chitosan—An overview. Int. J. Biol. Macromol., 2008, 43(3), 221-225.
Thakur, V.K.; Thakur, M.K. Recent advances in graft copolymerization and applications of chitosan: A review. ACS Sustain. Chem.& Eng., 2014, 2(12), 2637-2652.
Manoj, P.; Nayak, P.L. Graft copolymerization of methyl acrylate on chitosan: Initiated by ceric ammonium nitrate as the initiator-characterization and antimicrobial activity. Adv. Appl. Sci. Res, 2012, 3(3), 1646-1654.
Jayakumar, R.; Prabaharan, M.; Reis, R.L.; Mano, J. Graft copolymerized chitosan—present status and applications. Carbohydr. Polym., 2005, 62(2), 142-158.
Zohuriaan-Mehr, M.J. Advances in chitin and chitosan modification through graft copolymerization: A comprehensive review. Iran. Polym. J., 2005, 14(3), 235-265.
Sabaa, M.W. Chitosan-g-Copolymers: Synthesis, Properties, and Applications.In Polysaccharide Based Graft Copolymers; Kalia, S.; Sabaa, M.W., Eds.; Springer Berlin Heidelberg, 2013, pp. 111-147.
Yao, F.; Chen, W.; Wang, H.; Liu, H.; Yao, K.; Sun, P.; Lin, H. A study on cytocompatible poly (chitosan-gL-lactic acid). Polymer., 2003, 44(21), 6435-6441.
Venkatrajah, B.; Pandidurai, V.; Rajendran, R.; Elayarajah, B.; Jenifer, J.; Ashokan, B.; Anand, N. Polymer biocomposite nanoparticles for sustained drug delivery. IJABPT., 2011, 2(2), 454-462.
Berger, J.; Reist, M.; Mayer, J.M.; Felt, O.; Peppas, N.A.; Gurny, R. Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur. J. Pharm. Biopharm., 2004, 57(1), 19-34.
Berger, J.; Reist, M.; Mayer, J.M.; Felt, O.; Gurny, R. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur. J. Pharm. Biopharm., 2004, 57(1), 35-52.
Mi, F.L.; Sung, H.W.; Shyu, S.S.; Su, C.C.; Peng, C.K. Synthesis and characterization of biodegradable TPP/genipin co-crosslinked chitosan gel beads. Polymer., 2003, 44(21), 6521-6530.
Muzzarelli, R.A. Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids. Carbohydr. Polym., 2009, 77(1), 1-9.
Mi, F.L.; Shyu, S.S.; Peng, C. Characterization of ring-opening polymerization of genipin and pH-dependent cross-linking reactions between chitosan and genipin. J. Polym. Sci. A Polym. Chem., 2005, 43(10), 1985-2000.
Ostrowska-Czubenko, J.; Pieróg, M. Synthesis and characteristics of chemically modified chitosan membranes with sulfuric acid. Pol. J. Appl. Chem., 2009, 53(2), 155-160.
Ostrowska-Czubenko, J.; Pieróg, M.; Gierszewska-Drużyńska, M. Equilibrium swelling behavior of crosslinked chitosan hydrogels. Pol. J. Appl. Chem, 2011, 55(2), 49-56.
Dutta, P.K., Ed.; Chitin and chitosan for regenerative medicine; New York, NY, USA Springer, 2014.
Mourya, V.K.; Inamdar, N.N.; Choudhari, Y.M. Chitooligosaccharides: Synthesis, characterization and applications. Polym. Sci. Ser. A Chem. Phys., 2011, 53(7), 583-612.
Lodhi, G.; Kim, Y.S.; Hwang, J.W.; Kim, S.K.; Jeon, Y.J.; Je, J.Y.; Park, P.J. Chitooligosaccharide and its derivatives: preparation and biological applications. BioMed Res. Int., 2014, 2014, 654913.
Aam, B.B.; Heggset, E.B.; Norberg, A.L.; Sørlie, M.; Vårum, K.M.; Eijsink, V.G. Production of chitooligosaccharides and their potential applications in medicine. Mar. Drugs, 2010, 8(5), 1482-1517.
Kim, S.K.; Rajapakse, N. Enzymatic production and biological activities of chitosan oligosaccharides (COS): A review. Carbohydr. Polym., 2005, 62(4), 357-368.
Modrzejewska, Z.; Dorabialska, M.; Zarzycki, R.; Wojtasz-Pająk, A. The mechanism of sorption of Ag+ ions on chitosan microgranules: IR and NMR studies. Prog. Chem. Appl. Chitin Deriv., 2009, 14, 49-64.
Nie, J.; Wang, Z.; Hu, Q. Chitosan hydrogel structure modulated by metal ions. Sci. Rep., 2016, 6, 36005.
Gaisford, S.; Beezer, A.E.; Bishop, A.H.; Walker, M.; Parsons, D. An in vitro method for the quantitative determination of the antimicrobial efficacy of silver-containing wound dressings. Int. J. Pharm., 2009, 366(1-2), 111-116.
Meaume, S.; Vallet, D.; Nguyen Morere, M.; Teot, L. Evaluation of a silver-releasing hydroalginate dressing in chronic wounds with signs of local infection. J. Wound Care, 2005, 14(9), 411-419.
Ong, S.Y.; Wu, J.; Moochhala, S.M.; Tan, M.H.; Lu, J. Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties. Biomaterials, 2008, 29(32), 4323-4332.
Ip, M.; Lui, S.L.; Poon, V.K.; Lung, I.; Burd, A. Antimicrobial activities of silver dressings: An in vitro comparison. J. Med. Microbiol., 2006, 55(1), 59-63.
Said, J.; Dodoo, C.C.; Walker, M.; Parsons, D.; Stapleton, P.; Beezer, A.E.; Gaisford, S. An in vitro test of the efficacy of silver-containing wound dressings against Staphylococcus aureus and Pseudomonas aeruginosa in simulated wound fluid. Int. J. Pharm., 2014, 462(1-2), 123-128.
Percival, S.L.; Bowler, P.G.; Russell, D. Bacterial resistance to silver in wound care. J. Hosp. Infect., 2005, 60(1), 1-7.
Atiyeh, B.S.; Costagliola, M.; Hayek, S.N.; Dibo, S.A. Effect of silver on burn wound infection control and healing: Review of the literature. Burns, 2007, 33(2), 139-148.
Katsumiti, A.; Gilliland, D.; Arostegui, I.; Cajaraville, M.P. Mechanisms of toxicity of Ag nanoparticles in comparison to bulk and ionic Ag on mussel hemocytes and gill cells. PLoS One, 2015, 10(6), e0129039.
Vazquez-Muñoz, R.; Borrego, B.; Juárez-Moreno, K.; García-García, M.; Morales, J.D.M.; Bogdanchikova, N.; Huerta-Saquero, A. Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter? Toxicol. Lett., 2017, 276, 11-20.
Takenaka, S.; Karg, E.; Roth, C.; Schulz, H.; Ziesenis, A.; Heinzmann, U.; Heyder, J. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ. Health Perspect., 2001, 109(4), 547-551.
Cheung, R.C.F.; Ng, T.B.; Wong, J.H.; Chan, W.Y. Chitosan: An update on potential biomedical and pharmaceutical applications. Mar. Drugs, 2015, 13(8), 5156-5186.
No, H.K.; Park, N.Y.; Lee, S.H.; Meyers, S.P. Antibacterial activity of chitosans and chitosan oligomers with different molecular weights. Int. J. Food Microbiol., 2002, 74(1-2), 65-72.
Kumar, A.B.V.; Varadaraj, M.C.; Gowda, L.R.; Tharanathan, R.N. Characterization of chito-oligosaccharides prepared by chitosanolysis with the aid of papain and Pronase, and their bactericidal action against Bacillus cereus and Escherichia coli. Biochem. J., 2005, 391(2), 167-175.
Jeon, Y.J.; Park, P.J.; Kim, S.K. Antimicrobial effect of chitooligosaccharides produced by bioreactor. Carbohydr. Polym., 2001, 44(1), 71-76.
Dai, T.; Tanaka, M.; Huang, Y.Y.; Hamblin, M.R. Chitosan preparations for wounds and burns: Antimicrobial and wound-healing effects. Expert Rev. Anti Infect. Ther., 2011, 9(7), 857-879.
Sahariah, P.; Masson, M. Antimicrobial chitosan and chitosan derivatives: A review of the structure activity relationship. Biomacromolecules, 2017, 18(11), 3846-3868.
Zheng, L.Y.; Zhu, J.F. Study on antimicrobial activity of chitosan with different molecular weights. Carbohydr. Polym., 2003, 54(4), 527-530.
Muzzarelli, R.; Tarsi, R.; Filippini, O.; Giovanetti, E.; Biagini, G.; Varaldo, P.E. Antimicrobial properties of N-carboxybutyl chitosan. Antimicrob. Agents Chemother., 1990, 34(10), 2019-2023.
Sudarshan, N.R.; Hoover, D.G.; Knorr, D. Antibacterial action of chitosan. Food Biotechnol., 1992, 6(3), 257-272.
Liu, N.; Chen, X.G.; Park, H.J.; Liu, C.G.; Liu, C.S.; Meng, X.H.; Yu, L.J. Effect of MW and concentration of chitosan on antibacterial activity of Escherichia coli. Carbohydr. Polym., 2006, 64(1), 60-65.
Kong, M.; Chen, X.G.; Xing, K.; Park, H.J. Antimicrobial properties of chitosan and mode of action: A state of the art review. Int. J. Food Microbiol., 2010, 144, 51-63.
Park, S.C.; Nam, J.P.; Kim, J.H.; Kim, Y.M.; Nah, J.W.; Jang, M.K. Antimicrobial action of water-soluble beta-chitosan against clinical multi-drug resistant bacteria. Int. J. Mol. Sci., 2015, 16, 7995-8007.
Sahariah, P.; Benediktssdottir, B.E.; Hjalmarsdottir, M.A.; Sigurjonsson, O.E.; Sorensen, K.K.; Thygesen, M.B.; Jensen, K.J.; Masson, M. Impact of chain length on antibacterial activity and hemocompatibility of quaternary N-alkyl and N,N-dialkyl chitosan derivatives. Biomacromolecules, 2015, 16, 1449-1460.
Sarhan, W.A.; Azzazy, H.M. High concentration honey chitosan electrospun nanofibers: Biocompatibility and antibacterial effects. Carbohydr. Polym., 2015, 122, 135-143.
Chung, Y.C.; Wang, H.L.; Chen, Y.M.; Li, S.L. Effect of abiotic factors on the antibacterial activity of chitosan against waterborne pathogens. Bioresour. Technol., 2003, 88(3), 179-184.
Rhoades, J.; Roller, S. Antimicrobial actions of degraded and native chitosan against spoilage organisms in laboratory media and foods. Appl. Environ. Microbiol., 2000, 66, 80-86.
Younes, I.; Sellimi, S.; Rinaudo, M.; Jellouli, K.; Nasri, M. Influence of acetylation degree and molecular weight of homogeneous chitosans on antibacterial and antifungal activities. Int. J. Food Microbiol., 2014, 185, 57-63.
Tayel, A.A.; Moussa, S.H.; Salem, M.F.; Mazrou, K.E.; El‐Tras, W.F. Control of citrus molds using bioactive coatings incorporated with fungal chitosan/plant extracts composite. J. Sci. Food Agric., 2016, 96(4), 1306-1312.
Ben-Shalom, N.; Ardi, R.; Pinto, R.; Aki, C.; Fallik, E. Controlling gray mould caused by Botrytis cinerea in cucumber plants by means of chitosan. Crop Prot., 2003, 22, 285-290.
Atia, M.M.M.; Buchenauer, H.; Aly, A.Z.; Abou-Zaid, M.I. Antifungal activity of chitosan against Phytophthora infestans and activation of defence mechanisms in tomato to late blight. Biol. Agric. Hortic., 2005, 23, 175-197.
Saharan, V.; Sharma, G.; Yadav, M.; Choudhary, M.K.; Sharma, S.S.; Pal, A.; Raliya, R.; Biswas, P. Synthesis and in vitro antifungal efficacy of Cu-chitosan nanoparticles against pathogenic fungi of tomato. Int. J. Biol. Macromol., 2015, 75, 346-353.
El Ghaouth, A.; Arul, J.; Grenier, J.; Asselin, A. Antifungal activity of chitosan on two postharvest pathogens of strawberry fruits. Phytopathology, 1992, 82(4), 398-402.
Wang, L.S.; Wang, C.Y.; Yang, C.H.; Hsieh, C.L.; Chen, S.Y.; Shen, C.Y.; Wang, J.J.; Huang, K.S. Synthesis and anti-fungal effect of silver nanoparticles-chitosan composite particles. Int. J. Nanomedicine, 2015, 10, 2685-2696.
Lopez-Moya, F.; Colom-Valiente, M.F.; Martinez-Peinado, P.; Martinez-Lopez, J.E.; Puelles, E.; Sempere-Ortells, J.M.; Lopez-Llorca, L.V. Carbon and nitrogen limitation increase chitosan antifungal activity in Neurospora crassa and fungal human pathogens. Fungal Biol., 2015, 119, 154-169.
Gabriel Jdos, S.; Tiera, M.J.; Tiera, V.A. Synthesis, characterization, and antifungal activities of amphiphilic derivatives of diethylaminoethyl chitosan against Aspergillus flavus. J. Agric. Food Chem., 2015, 63, 5725-5731.
Bai, R.K.; Huang, M.Y.; Jiang, Y.Y. Selective permeabilities of chitosan-acetic acid complex membrane and chitosan-polymer complex membranes for oxygen and carbon dioxide. Polym. Bull., 1988, 20(1), 83-88.
Karagozlu, M.Z.; Karadeniz, F.; Kim, S.K. Anti-HIV activities of novel synthetic peptide conjugated chitosan oligomers. Int. J. Biol. Macromol., 2014, 66, 260-266.
Artan, M.; Karadeniz, F.; Karagozlu, M.Z.; Kim, M.M.; Kim, S.K. Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides. Carbohydr. Res., 2010, 345, 656-662.
Meng, J.; Zhang, T.; Agrahari, V.; Ezoulin, M.J.; Youan, B.B. Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention. Nanomedicine., 2014, 9, 1595-1612.
Aghasadeghi, M.R. Heidari. H.; Sadat, S.M.; Irani, S.; Amini, S.; Siadat, S.D.; Fazlhashemy, M.E.; Zabihollahi, R.; Atyabi, S.M.; Momen, S.B. Lamivudine-PEGylated chitosan: A novel effective nanosized antiretroviral agent. Curr. HIV Res., 2013, 11, 309-320.
Khan, A.B.; Thakur, R.S. Formulation and evaluation of mucoadhesive microspheres of tenofovir disoproxil fumarate for intravaginal use. Curr. Drug Deliv., 2014, 11, 112-122.
Ramana, L.N.; Sharma, S.; Sethuraman, S.; Ranga, U.; Krishnan, U.M. Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems. Biochim. Biophys. Acta, 2014, 1840, 476-484.
Belletti, D.; Tosi, G.; Forni, F.; Gamberini, M.C.; Baraldi, C.; Vandelli, M.A.; Ruozi, B. Chemico-physical investigation of tenofovir loaded polymeric nanoparticles. Int. J. Pharm., 2012, 436, 753-763.
Meng, J.; Sturgis, T.F.; Youan, B.B. Engineering tenofovir loaded chitosan nanoparticles to maximize microbicide mucoadhesion. Eur. J. Pharm. Sci., 2011, 44, 57-67.
Yang, L.; Chen, L.; Zeng, R.; Li, C.; Qiao, R.; Hu, L.; Li, Z. Synthesis, nanosizing and in vitro drug release of a novel anti-HIV polymeric prodrug: Chitosan-O-isopropyl-5′-O-d4T monophosphate conjugate. Bioorg. Med. Chem., 2010, 18, 117-123.
Tokoro, A.; Tatewaki, N.; Suzuki, K.; Mikami, T.; Suzuki, S.; Suzuki, M. Growth-inhibitory effect of hexa-N-acetylchitohexaose and chitohexaose against Meth-A solid tumor. Chem. Pharm. Bull., 1988, 36, 784-790.
Lin, S.Y.; Chan, H.Y.; Shen, F.H.; Chen, M.H.; Wang, Y.J.; Yu, C.K. Chitosan prevents the development of AOM-induced aberrant crypt foci in mice and suppressed the proliferation of AGS cells by inhibiting DNA synthesis. J. Cell. Biochem., 2007, 100, 1573-1580.
Gibot, L.; Chabaud, S.; Bouhout, S.; Bolduc, S.; Auger, F.A.; Moulin, V.J. Anticancer properties of chitosan on human melanoma are cell line dependent. Int. J. Biol. Macromol., 2015, 72, 370-379.
Jiang, Z.; Han, B.; Li, H.; Li, X.; Yang, Y.; Liu, W. Preparation and anti-tumor metastasis of carboxymethyl chitosan. Carbohydr. Polym., 2015, 125, 53-60.
Park, J.K.; Chung, M.J.; Choi, H.N.; Park, Y.I. Effects of the molecular weight and the degree of deacetylation of chitosan oligosaccharides on antitumor activity. Int. J. Mol. Sci., 2011, 12, 266-277.
He, B.; Tao, H.Y.; Liu, S.Q. Neuroprotective effects of carboxymethylated chitosan on hydrogen peroxide induced apoptosis in Schwann cells. Eur. J. Pharmacol., 2014, 740, 127-134.
Ruiz, G.A.M.; Corrales, H.F.Z. Chitosan, chitosan derivatives and their biomedical applications in biological activities and application of marine polysaccharides; InTech, 2017, pp. 87-106.
Pokhrel, S.; Yadav, P.N.; Adhikari, R. Applications of chitin and chitosan in industry and medical science: A review. Nep. J. Sci. Technol, 2015, 16(1), 99-104.
Silva, S.S.; Mano, J.F.; Reis, R.L. Ionic liquids in the processing and chemical modification of chitin and chitosan for biomedical applications. Green Chem., 2017, 19(5), 1208-1220.
Zhang, J.; Xia, W.; Liu, P.; Cheng, Q.; Tahi, T.; Gu, W.; Li, B. Chitosan modification and pharmaceutical/biomedical applications. Mar. Drugs, 2010, 8(7), 1962-1987.
Elieh-Ali-Komi, D.; Hamblin, M.R. Chitin and chitosan: Production and application of versatile biomedical nanomaterials. Int. J. Adv. Res., 2016, 4(3), 411-427.
Kim, I.Y.; Seo, S.J.; Moon, H.S.; Yoo, M.K.; Park, I.Y.; Kim, B.C.; Cho, C.S. Chitosan and its derivatives for tissue engineering applications. Biotechnol. Adv., 2008, 26, 1-21.
Yang, T.L. Chitin-based materials in tissue engineering: Applications in soft tissue and epithelial organ. Int. J. Mol. Sci., 2011, 12(3), 1936-1963.
Muzzarelli, R.A. Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydr. Polym., 2009, 76(2), 167-182.
Chen, X.G.; Wang, Z.; Liu, W.S.; Park, H.J. The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. Biomaterials, 2002, 23(23), 4609-4614.
Liu, X.; Ma, L.; Liang, J.; Zhang, B.; Teng, J.; Gao, C. RNAi functionalized collagen-chitosan/silicone membrane bilayer dermal equivalent for full-thickness skin regeneration with inhibited scarring. Biomaterials, 2013, 34(8), 2038-2048.
Li, B.; Wang, L.; Xu, F.; Gang, X.; Demirci, U.; Wei, D.; Li, Y.; Feng, Y.; Jia, D.; Zhou, Y. Hydrosoluble, UV-crosslinkable and injectable chitosan for patterned cell-laden microgel and rapid transdermal curing hydrogel in vivo. Acta Biomater., 2015, 22, 59-69.
Yang, L.; Wang, Q.; Peng, L.; Yue, H.; Zhang, Z. Vascularization of repaired limb bone defects using chitosan-β-tricalcium phosphate composite as a tissue engineering bone scaffold. Mol. Med. Rep., 2015, 12, 2343-2347.
Frohbergh, M.E.; Katsman, A.; Botta, G.P.; Lazarovici, P.; Schauer, C.L.; Wegst, U.G.; Lelkes, P.I. Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering. Biomaterials, 2012, 33(36), 9167-9178.
Li, Q.; Zhou, G.; Yu, X.; Wang, T.; Xi, Y.; Tang, Z. Porous deproteinized bovine bone scaffold with three-dimensional localized drug delivery system using chitosan microspheres. Biomed. Eng. Online, 2015, 14, 33.
Correia, C.O.; Leite, A.J.; Mano, J.F. Chitosan/bioactive glass nanoparticles scaffolds with shape memory properties. Carbohydr. Polym., 2015, 123, 39-45.
Li, H. ; Hu, C. ; H. Yu, C. Chen Chitosan composite scaffolds for articular cartilage defect repair: A review. RSC Advances, 2018, 8, 3736-3749.
Chameettachal, S.; Murab, S.; Vaid, R.; Midha, S.; Ghosh, S. Effect of visco-elastic silk-chitosan microcomposite scaffolds on matrix deposition and biomechanical functionality for cartilage tissue engineering. J. Tissue Eng. Regen. Med., 2017, 11(4), 1212-1229.
Shapira, Y.; Tolmasov, M.; Nissan, M.; Reider, E.; Koren, A.; Biron, T.; Rochkind, S. Comparison of results between chitosan hollow tube and autologous nerve graft in reconstruction of peripheral nerve defect: An experimental study. Microsurgery, 2016, 36(8), 664-671.
Tanaka, N.; Matsumoto, I.; Suzuki, M.; Kaneko, M.; Nitta, K.; Seguchi, R.; Ooi, A.; Takemura, H. Chitosan tubes can restore the function of resected phrenic nerves. Interact. Cardiovasc. Thorac. Surg., 2015, 21, 8-13.
Mincea, M.; Negrulescu, A.; Ostafe, V. Preparation, modification, and applications of chitin nanowhiskers: A review. Rev. Adv. Mater. Sci., 2012, 30(3), 225-242.
Jian, R.; Yixu, Y.; Sheyu, L.; Jianhong, S.; Yaohua, Y.; Xing, S.; Fangling, X. Repair of spinal cord injury by chitosan scaffold with glioma ECM and SB216763 implantation in adult rats. J. Biomed. Mater. Res. A, 2015, 103(10), 3259-3272.
Ways, T.M.; Lau, W.M.; Khutoryanskiy, V.V. Chitosan and its derivatives for application in mucoadhesive drug delivery system. Polymers., 2018, 10(3), 267.
Jabbal-Gill, I.; Watts, P.; Smith, A. Chitosan-based delivery systems for mucosal vaccines. Expert Opin. Drug Deliv., 2012, 9, 1051-1067.
Xing, L.; Fan, Y.T.; Zhou, T.J.; Gong, J.H.; Cui, L.H.; Cho, K.H.; Cho, C.S. Chemical modification of chitosan for efficient vaccine delivery. Molecules, 2018, 23(2), 229.
Kofuji, K.; Qian, C.J.; Nishimura, M.; Sugiyama, I.; Murata, Y.; Kawashima, S. Relationship between physicochemical characteristics and functional properties of chitosan. Eur. Polym. J., 2005, 41, 2784-2791.
Sinha, V.R.; Singla, A.K.; Wadhawan, S.; Kaushik, R.; Kumria, R.; Bansal, K.; Dhawan, S. Chitosan microspheres as a potential carrier for drugs. Int. J. Pharm., 2004, 274(1-2), 1-33.
Pandey, R.; Khuller, G.K. Chemotherapeutic potential of alginate–chitosan microspheres as anti-tubercular drug carriers. J. Antimicrob. Chemother., 2004, 53(4), 635-640.
Berthold, A.; Cremer, K.; Kreuter, J.S.T.P. Preparation and characterization of chitosan microspheres as drug carrier for prednisolone sodium phosphate as model for anti-inflammatory drugs. J. Control. Release, 1996, 39(1), 17-25.
Jiang, H.L.; Park, I.K.; Shin, N.R.; Kang, S.G.; Yoo, H.S.; Kim, S.I.; Suh, S.B.; Akaike, T.; Cho, C.S. In vitro study of the immune stimulating activity of an atrophic rhinitis vaccine associated to chitosan microspheres. Eur. J. Pharm. Biopharm., 2004, 58, 471-476.
Thanou, M.; Verhoef, J.C.; Junginger, H.E. Oral drug absorption enhancement by chitosan and its derivatives. Adv. Drug Deliv. Rev., 2001, 52, 117-126.
del Valle, L.J.; Díaz, A.; Puiggalí, J. Hydrogels for biomedical applications: Cellulose, chitosan, and protein/peptide derivatives. Gels,, 2017, 3, (3), pii: E27.
Supper, S.; Anton, N.; Boisclair, J.; Seidel, N.; Riemenschnitter, M.; Curdy, C.; Vandamme, T. Chitosan/glucose 1-phosphate as new stable in situ forming depot system for controlled drug delivery. Eur. J. Pharm. Biopharm., 2014, 88, 361-373.
Supper, S.; Anton, N.; Seidel, N.; Riemenschnitter, M.; Curdy, C.; Vandamme, T. Thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives in pharmaceutical and biomedical applications. Expert Opin. Drug Deliv., 2014, 11, 249-267.
Lai, P.; Daear, W.; Lobenberg, R.; Prenner, E.J. Overview of the preparation of organic polymeric nanoparticles for drug delivery based on gelatine, chitosan, poly(D,L-lactide-co-glycolic acid) and polyalkylcyanoacrylate. Colloids Surf. B Biointerfaces, 2014, 118, 154-163.
Hudson, D.; Margaritis, A. Biopolymer nanoparticle production for controlled release of biopharmaceuticals. Crit. Rev. Biotechnol., 2014, 34, 161-179.
Kato, Y.; Onishi, H.; Machida, Y. Contribution of chitosan and its derivatives to cancer chemotherapy. In Vivo, 2005, 19, 301-310.
Anraku, M.; Hiraga, A.; Iohara, D.; Pipkin, J.D.; Uekama, K.; Hirayama, F. Slow-release of famotidine from tablets consisting of chitosan/sulfobutyl ether beta-cyclodextrin composites. Int. J. Pharm., 2015, 487, 142-147.
Pereira, P.; Pedrosa, S.S.; Wymant, J.M.; Sayers, E.; Correia, A.; Vilanova, M.; Jones, A.T.; Gama, F.M. siRNA inhibition of endocytic pathways to characterize the cellular uptake mechanisms of folate-functionalized glycol chitosan nanogels. Mol. Pharm., 2015, 12, 1970-1979.
Kulkarni, N.; Wakte, P.; Naik, J. Development of floating chitosan-xanthan beads for oral controlled release of glipizide. Int. J. Pharm. Investig., 2015, 5, 73-80.
Al-Kurdi, Z.I.; Chowdhry, B.Z.; Leharne, S.A.; Al Omari, M.M.; Badwan, A.A. Low molecular weight chitosan-insulin polyelectrolyte complex: Characterization and stability studies. Mar. Drugs, 2015, 13, 1765-1784.
Gadalla, H.H.; Soliman, G.M.; Mohammed, F.A.; El-Sayed, A.M. Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone. Drug Deliv., 2015, 8, 1-14.
Jana, S.; Laha, B.; Maiti, S. Boswellia gum resin/chitosan polymer composites: Controlled delivery vehicles for aceclofenac. Int. J. Biol. Macromol., 2015, 77, 303-306.
Qinna, N.A.; Karwi, Q.G.; Al-Jbour, N.; Al-Remawi, M.A.; Alhussainy, T.M.; Al-So’ud, K.A.; Al Omari, M.M.; Badwan, A.A. Influence of molecular weight and degree of deacetylation of low molecular weight chitosan on the bioactivity of oral insulin preparations. Mar. Drugs, 2015, 13, 1710-1725.
Kim, K.; Ryu, J.H.; Lee, H. Chitosan-catechol: A polymer with long-lasting mucoadhesive properties. Biomaterials, 2015, 52, 161-170.
Chatterjee, S.; Judeh, Z.M.A. Encapsulation of fish oil with N-stearoyl O-butylglyceryl chitosan using membrane and ultrasonic emulsification processes. Carbohydr. Polym., 2015, 123, 432-442.
Jayasree, R.S.; Rathinam, K.; Sharma, C.P. Development of artificial skin (Template) and influence of different types of sterilization procedures on wound healing pattern in rabbits and guinea pigs. J. Biomater. Appl., 1995, 10, 144-162.
Ueno, H.; Mori, T.; Fujinaga, T. Topical formulations and wound healing applications of chitosan. Adv. Drug Deliv. Rev., 2001, 52, 105-115.
Muzzarelli, R.A.; Mattioli-Belmonte, M.; Pugnaloni, A.; Biagini, G. Biochemistry, histology and clinical uses of chitins and chitosans in wound healing. EXS, 1999, 87, 251-264.
Azuma, K.; Izumi, R.; Osaki, T.; Ifuku, S.; Morimoto, M.; Saimoto, H.; Minami, S.; Okamoto, Y. Chitin, chitosan, and its derivatives for wound healing: Old and new materials. J. Funct. Biomater., 2015, 6, 104-142.
Naseri, N.; Algan, C.; Jacobs, V.; John, M.; Oksman, K.; Mathew, A.P. Electrospun chitosan-based nanocomposite mats reinforced with chitin nanocrystals for wound dressing. Carbohydr. Polym., 2014, 109, 7-15.
Guo, R.; Xu, S.; Ma, L.; Huang, A.; Gao, C. Enhanced angiogenesis of gene-activated dermal equivalent for treatment of full thickness incisional wounds in a porcine model. Biomaterials, 2010, 31(28), 7308-7320.
Ishihara, M.; Obara, K.; Nakamura, S.; Fujita, M.; Masuoka, K.; Kanatani, Y.; Takase, B.; Hattori, H.; Morimoto, Y.; Ishihara, M. Chitosan hydrogel as a drug delivery carrier to control angiogenesis. J. Artif. Organs, 2006, 9, 8-16.
Chou, T.C.; Fu, E.; Wu, C.J.; Yeh, J.H. Chitosan enhances platelet adhesion and aggregation. Biochem. Biophys. Res. Commun., 2003, 302(3), 480-483.
Okamoto, Y.; Yano, R.; Miyatake, K.; Tomohiro, I.; Shigemasa, Y.; Minami, S. Effects of chitin and chitosan on blood coagulation. Carbohydr. Polym., 2003, 53(3), 337-342.
Biagini, G.; Bertani, A.; Muzzarelli, R.; Damadei, A.; DiBenedetto, G.; Belligolli, A.; Riccotti, G.; Zucchini, C.; Rizzoli, C. Wound management with N-carboxybutyl chitosan. Biomaterials, 1991, 12, 281-286.
Stone, C.A.; Wright, H.; Devaraj, V.S.; Clarke, T.; Powell, R. Healing at skin graft donor sites dressed with chitosan. Br. J. Plast. Surg., 2000, 53, 601-606.
Azad, A.K.; Sermsintham, N.; Chandrkrachang, S.; Stevens, W.F. Chitosan membrane as a wound-healing dressing: Characterization and clinical application. J. Biomed. Mater. Res. B Appl. Biomater., 2004, 69, 216-222.
Valentine, R.; Athanasiadis, T.; Moratti, S.; Hanton, L.; Robinson, S.; Wormald, P.J. The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery. Am. J. Rhinol. Allergy, 2010, 24, 70-75.
Bennett, B.L.; Littlejohn, L.F.; Kheirabadi, B.S.; Butler, F.K.; Kotwal, R.S.; Dubick, M.A.; Bailey, J.A. Management of external hemorrhage in tactical combat casualty care: Chitosan-based hemostatic gauze dressings-TCCC guidelines-change 13-05. J. Spec. Oper. Med., 2014, 14, 40-57.
Hatamabadi, H.R.; Zarchi, F.A.; Kariman, H.; Dolatabadi, A.A.; Tabatabaey, A.; Amini, A. Celox-coated gauze for the treatment of civilian penetrating trauma: A randomized clinical trial. Trauma Mon., 2015, 20(1), e23862.
Nguyen, N.; Hasan, S.; Caufield, L.; Ling, F.S.; Narins, C.R. Randomized controlled trial of topical hemostasis pad use for achieving vascular hemostasis following percutaneous coronary intervention. Catheter. Cardiovasc. Interv., 2007, 69, 801-807.
Weng, M.H. The effect of protective treatment in reducing pressure ulcers for non-invasive ventilation patients. Intensive Crit. Care Nurs., 2008, 24, 295-259.
Mohaiyiddin, M.S.; Ong, H.L.; Othman, M.B.H.; Julkapli, N.M.; Villagracia, A.R.C.; Akil, H.M. Swelling behavior and chemical stability of chitosan/nanocellulose biocomposites. Polym. Comp. Special Issue: Composites for Biological Applications, 2018, 39(S1), E561-E572.
Lamarra, J.; Damonte, L.; Rivero, S.; Pinotti, A. Structural insight into chitosan supports functionalized with nanoparticles. Adv. Mater. Sci. Eng., 2018, 3965783.
Capel, V.; Vllasaliu, D.; Watts, P.; Clarke, P.A.; Luxton, D.; Grabowska, A.M.; Mantovani, G.; Stolnik, S. Water-soluble substituted chitosan derivatives as technology platform for inhalation delivery of siRNA. Drug Deliv., 2018, 25(1), 644-653.
Ali, A. Ahmed. S. A review on chitosan and its nanocomposites in drug delivery. Int. J. Biol. Macromol., 2018, 109, 273-286.
Ahmed, S.; Annu, A.; Ali, A.; Sheikh, J. A review on chitosan centred scaffolds and their applications in tissue engineering. Int. J. Biol. Macromol., 2018, 116, 849-862.
Demina, T.S.; Gilman, A.B.; Akopova, T.A.; Zelenetskii, A.N. High Energy Chem., 2014, 48, 293-302.

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Year: 2019
Page: [737 - 750]
Pages: 14
DOI: 10.2174/1389557519666190112142735
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