• Eduardo Pereira De Azevedo Graduate Program in Biotechnology, Universidade Potiguar–UnP, Av. Senador Salgado Filho, 59080400, Natal RN, Brazil


Chitosan has been extensively used to prepare hydrogel systems. The fact that chemically and ionically crosslinked chitosan hydrogels can slowly release drugs through swelling have enabled their use in drug delivery applications. In addition, the high porosity of these hydrogels ensures a more effective cell loading and depending on the pore size and interconnectivity, it can lead to cell differentiation and eventually tissue formation. The purpose of this review is to take a closer look at the use of chitosan hydrogels to prepare drug delivery systems and scaffolds for tissue engineering. Aspects involving chitosan structure, physicochemical properties and biological applications are also discussed. In addition, this article reviews the methods used to prepare chitosan hydrogels and the mechanisms involved in the release of drugs.


Keywords: Chitosan, Hydrogels, Drug delivery, Tissue engineering


Download data is not yet available.


1. Singh A. External stimuli response on a novel chitosan hydrogel crosslinked with formaldehyde. Bull Mater Sci 2006;29:233.
2. Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Delivery Rev 2010;62:83-99.
3. Elviri L, Asadzadeh M, Cucinelli R, Bianchera A, Bettini R. Macroporous chitosan hydrogels: effects of sulfur on the loading and release behaviour of amino acid-based compounds. Carbohydr Polym 2015;132:50-8.
4. Rami L, Malaise S, Delmond S, Fricain JC, Siadous R, Schlaubitz S, et al. Physicochemical modulation of chitosan-based hydrogels induces different biological responses: interest for tissue engineering. J Biomed Mater Res Part A 2014;102:3666-76.
5. Vodna L, Bubenikova S, Lacik I, Chorvat DJr, Bakos D. Chitosan based hydrogel microspheres as drug carriers. Macromol Biosci 2007;7:629-34.
6. Zheng JN, Xie HG, Yu WT, Liu XD, Xie WY, Zhu J, et al. Chitosan-g-MPEG-modified alginate/chitosan hydrogel microcapsules: a quantitative study of the effect of polymer architecture on the resistance to protein adsorption. Langmuir 2010;26:17156-64.
7. Pashkunova-Martic I, Kremser C, Galanski M, Arion V, Debbage P, Jaschke W, et al. Lectin-Gd-loaded chitosan hydrogel nanoparticles: a new biospecific contrast agent for MRI. Mol Imaging Biol 2011;13:16-24.
8. Chatterjee S, Lee MW, Woo SH. Adsorption of congo red by chitosan hydrogel beads impregnated with carbon nanotubes. Bioresour Technol 2010;101:1800-6.
9. Chatterjee S, Lee DS, Lee MW, Woo SH. Enhanced molar sorption ratio for naphthalene through the impregnation of surfactant into chitosan hydrogel beads. Bioresour Technol 2010;101:4315-21.
10. Chatterjee S, Chatterjee T, Lim SR, Woo SH. Effect of the addition mode of carbon nanotubes for the production of chitosan hydrogel core-shell beads on adsorption of Congo red from aqueous solution. Bioresour Technol 2011;102:4402-9.
11. Horio T, Ishihara M, Fujita M, Kishimoto S, Kanatani Y, Ishizuka T, et al. Effect of photo crosslinkable chitosan hydrogel and its sponges to stop bleeding in a rat liver injury model. Artif Organs 2010;34:342-7.
12. Ribeiro MP, Espiga A, Silva D, Baptista P, Henriques J, Ferreira C, et al. Development of a new chitosan hydrogel for wound dressing. Wound Repair Regeneration 2009;17:817-24.
13. Zhang Y, Ji C. Electro-induced covalent cross-linking of chitosan and formation of chitosan hydrogel films: its application as an enzyme immobilization matrix for use in a phenol sensor. Anal Chem 2010;82:5275-81.
14. Leipzig ND, Wylie RG, Kim H, Shoichet MS. Differentiation of neural stem cells in three-dimensional growth factor-immobilized chitosan hydrogel scaffolds. Biomaterials 2011;32:57-64.
15. Madhumathi K, Shalumon KT, Rani VV, Tamura H, Furuike T, Selvamurugan N, et al. Wet chemical synthesis of chitosan hydrogel-hydroxyapatite composite membranes for tissue engineering applications. Int J Biol Macromol 2009;45:12-5.
16. Hong Y, Gong Y, Gao C, Shen J. Collagen-coated polylactide microcarriers/chitosan hydrogel composite: injectable scaffold for cartilage regeneration. J Biomed Mater Res Part A 2008;85:628-37.
17. Yan XZ, van den Beucken JJ, Cai X, Yu N, Jansen JA, Yang F. Periodontal tissue regeneration using enzymatically solidified chitosan hydrogels with or without cell loading. Tissue Eng Part A 2015;21:1066-76.
18. Berger J, Reist M, Mayer JM, Felt O, Gurny R. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur J Pharm Biopharm 2004;57:35-52.
19. Hoffmann B, Seitz D, Mencke A, Kokott A, Ziegler G. Glutaraldehyde and oxidised dextran as crosslinker reagents for chitosan-based scaffolds for cartilage tissue engineering. J Mater Sci Mater Med 2009;20:1495-503.
20. Knaul JZ, Hudson SM, Creber KAM. Crosslinking of chitosan fibers with dialdehydes: proposal of a new reaction mechanism. J Polym Sci Part B: Polym Phys 1999;37:1079-94.
21. Debnath T, Ghosh S, Potlapuvu US, Kona L, Kamaraju SR, Sarkar S, et al. Proliferation and differentiation potential of human adipose-derived stem cells grown on chitosan hydrogel. PLoS One 2015;10. doi: 10.1371/journal.pone.0120803. [Article in Press]
22. Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymer 2008;49:1993-2007.
23. Zou X, Zhao X, Ye L. Synthesis of cationic chitosan hydrogel and its controlled glucose-responsive drug release behavior. Chem Eng J 2015;273:92-100.
24. Han HD, Song CK, Park YS, Noh KH, Kim JH, Hwang T, et al. A chitosan hydrogel-based cancer drug delivery system exhibits synergistic antitumor effects by combining with a vaccinia viral vaccine. Int J Pharm 2008;350:27-34.
25. Kalshetti PP, Rajendra VB, Dixit DN, Parekh PP. Hydrogels as a drug delivery system and applications: a review. Int J Pharm Pharm Sci 2012;4:1-7.
26. Madihally SV, Matthew HW. Porous chitosan scaffolds for tissue engineering. Biomaterials 1999;20:1133-42.
27. Ravi Kumar MNV. A review of chitin and chitosan applications. React Funct Polym 2000;46:1-27.
28. Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci 2006;31:603-32.
29. Prabaharan M. Review paper: chitosan derivatives as promising materials for controlled drug delivery. J Biomater Appl 2008;23:5-36.
30. Dutta PK, Dutta J, Tripathi VS. Chitin and chitosan: chemistry, properties and applications. J Sci Ind Res 2004;63:20-31.
31. Kas HS. Chitosan: properties, preparations and application to microparticulate systems. J Microencapsulation 1997;14:689-711.
32. Laranjeira MCM, Fávere VT. Quitosana: biopolímero functional com potencial industrial biomédico. Quim Nova 2009;32:672-8.
33. Aranaz I, Mengibar M, Harris R, Panos I, Miralles B, Acosta N, et al. Functional characterization of chitin and chitosan. Curr Chem Biol 2009;3:203-30.
34. Koide SS. Chitin-chitosan: properties, benefits and risks. Nutr Res 1998;18:1091-101.
35. No HK, Park NY, Lee SH, Meyers SP. Antibacterial activity of chitosans and chitosan oligomers with different molecular weights. Int J Food Microbiol 2002;74:65-72.
36. Lin CC, Metters AT. Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Delivery Rev 2006;58:1379-408.
37. Kim SW, Bae YH, Okano T. Hydrogels: swelling, drug loading, and release. Pharm Res 1992;9:283-90.
38. Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discovery Today 2002;7:569-79.
39. Wichterle O, Lim D. Hydrophilic gels in biological use. Nature 1960;185:117.
40. Kim GO, Kim N, Kim da Y, Kwon JS, Min BH. An electrostatically crosslinked chitosan hydrogel as a drug carrier. Molecules 2012;17:13704-11.
41. Tronci G, Ajiro H, Russell SJ, Wood DJ, Akashi M. Tunable drug-loading capability of chitosan hydrogels with varied network architectures. Acta Biomater 2014;10:821-30.
42. Malaise S, Rami L, Montembault A, Alcouffe P, Burdin B, Bordenave L, et al. Bioresorption mechanisms of chitosan physical hydrogels: a scanning electron microscopy study. Mater Sci Eng C 2014;42:374-84.
43. Das N. Preparation methods and properties of hydrogel: a review. Int J Pharm Pharm Sci 2013;5:112-7.
44. Baran ET, Mano JF, Reis RL. Starch-chitosan hydrogels prepared by reductive alkylation cross-linking. J Mater Sci Mater Med 2004;15:759-65.
45. Li F, Liu WG, Yao KD. Preparation of oxidized glucose-crosslinked N-alkylated chitosan membrane and in vitro studies of pH-sensitive drug delivery behaviour. Biomaterials 2002;23:343-7.
46. Moura MJ. Rheological study of genip in cross-linked chitosan hydrogels. Biomacromolecules 2007;8:3823-9.
47. Muzzarelli RAA. Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids. Carbohydr Polym 2009;77:1-9.
48. Pourjavadi A, Aghajani V, Ghasemzadeh H. Synthesis, characterization and swelling behavior of chitosan-sucrose as a novel full-polysaccharide superabsorbent hydrogel. J Appl Polym Sci 2008;109:2648-55.
49. Azevedo EP, Santhana Mariappan SV, Kumar V. Preparation and characterization of chitosans carrying aldehyde functions generated by nitrogen oxides. Carbohydr Polym 2012;87:1925-32.
50. Ishihara M, Obara K, Nakamura S, Fujita M, Masuoka K, Kanatani Y, et al. Chitosan hydrogel as a drug delivery carrier to control angiogenesis. J Artif Organs 2006;9:8-16.
51. Azevedo EP, Kumar V. Rheological, water uptake and controlled release properties of a novel self-gelling aldehyde functionalized chitosan. Carbohydr Polym 2012;90:894-900.
52. Senel S, Ikinci G, Kas S, Yousefi-Rad A, Sargon MF, Hincal AA. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 2000;193:197-203.
53. Ruel-Gariepy E, Shive M, Bichara A, Berrada M, Le Garrec D, Chenite A, et al. A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel. Eur J Pharm Biopharm 2004;57:53-63.
54. Balakrishnan B, Jayakrishnan A. Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds. Biomaterials 2005;26:3941-51.
55. Harley BA, Hastings AZ, Yannas IV, Sannino A. Fabricating tubular scaffolds with a radial pore size gradient by a spinning technique. Biomaterials 2006;27:866-74.
56. Costa Jr ES, Mansur HS. Preparação e caracterização de blendas de quitosana/poli(álcool vinílico) reticuladas quimicamente com glutaraldeído para aplicação em engenharia de tecido. Quim Nova 2008;31:1460-6.
57. Hsieh W, Chang C, Lin S. Morphology and characterization of 3D micro-porous structured chitosan scaffolds for tissue engineering. Colloids Surf B 2007;57:250-5.
58. Harley BA, Hastings AZ, Yannas IV, Sannino A. Fabricating tubular scaffolds with a radial pore size gradient by a spinning technique. Biomaterials 2006;27:866-74.
59. Song Y, Wennink JWH, Kamphuis MMJ, Vermes I, Poot AA, Feijen J, et al. Effective seeding of smooth muscle cells into tubular poly(trimethylene carbonate) scaffolds for vascular tissue engineering. J Biomed Mater Res A 2010;95A:440-6.
60. Zeltinger J, Sherwood JK, Graham DA, Mueller R, Griffith LG. Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. Tissue Eng 2001;7:557-72.
61. Park IS, Kim SH, Kim IH, Kim SH. A collagen/smooth muscle cell-incorporated elastic scaffold for tissue-engineered vascular grafts. J Biomater Sci Polym Ed 2009;20:1645-60.
1061 Views | 3071 Downloads
How to Cite
Azevedo, E. P. D. “CHITOSAN HYDROGELS FOR DRUG DELIVERY AND TISSUE ENGINEERING APPLICATIONS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 12, Oct. 2015, pp. 8-14,
Review Article(s)