CHITOSAN: A MULTIFACET POLYMER
Objective: Chitosan is considerably versatile and promising biomaterial. It is a natural, tough, cationic, nontoxic, biodegradable, and biocompatible polymer obtained by alkaline deacetylation of chitin. Chitin is a polysaccharide obtained from exoskeletons of crustaceans and sea insects such as crab, krill, shrimp and crawfish etc. Besides the formerly mentioned resources it is also obtained from some fungi and bacterial cell walls.
Methods: Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating, stabilizing, suspending, tablet coating, and film forming material. Chitosan has been comprehensively investigated for its suitability for its controlled release characteristics in various studies. Chitosan presents remarkable absorption and penetration enhancing properties that makes it a good candidate for the delivery of genes and peptide.
Results: It is possessing tremendous mucoadhesive and inherent anti-microbial properties, so that it can be used as a carrier for novel drug delivery. In addition to the above mentioned reasons, tailoring the controlled release and to improve the therapeutic efficacy of the low molecular weight drug compounds can also be achieved by this polymer and moreover in combination with various polymers is feasible due its compatibility i.e. low chemical reactivity.
Conclusion: This brief editorial epitomizes the potential application of chitosan in the development of drug delivery systems.Keywords: Chitosan, Drug delivery, Gene delivery, Pharmaceutical applications.
2. Paul W, Sharma CP. Chitosan, a drug carrier for the 21st century: a review, STP. Pharma Sci 2000;10:5-22.
3. Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm Res 1998;15(9):1326-31.
4. Wenshui X, Ping L, Jiali Z, Jie C. Biological activities of chitosan and chit oligosaccharides. Food Hydrocolloids 2011;25:170-9.
5. Knorr D. Use of chitinous polymers in food: A challenge for food research and development. Food Technol 1984;38:85-9.
6. Shaji J, Jain V, Lodha S. Chitosan: a novel pharmaceutical excipient. Int J Pharm Appl Sci 2010;1(1):11-28.
7. Kofuji K, Qian CJ, Nishimura M, Sugiyama I, Murata Y, Kawashima S. Relationship between physicochemical characteristics and functional properties of chitosan. Eur Polym J 2005;41(11):2784-91.
8. Averbach BL. Film-forming capability of chitosan. In: Muzzarelli RAA, Pariser ER. editors. Proceedings of the first international conference on Chitin/Chitosan. MIT: Cambridge, MA; 1978. p. 199-209.
9. Dhanikula AB, Panchagnula R. Development and characterization of biodegradable chitosan films for local delivery of paclitaxel. AAPS J 2004;6(3):1-12.
10. Muzzarelli RAA. Filmogenic properties of Chitin/Chitosan' in Chitin. In: Nature and technology. Muzzarelli RAA, Jeuniaux C, Gooday GW, Eds. Plenum Press: New York; 1986. p. 389-96.
11. Park JW, Choi KH, Park KP. Acid-base equilibria and related properties of chitosan. Bull Korean Chem Soc 1983;4(2):68-72.
12. Bansal V, Sharma PK, Sharma N, Pal OP, Malviya R. Applications of chitosan and chitosan derivatives in drug delivery. Adv Bio Res 2011;5(1):28-37.
13. Gupta H, Velpandian T, Jain S. Ion-and pH-activated novel in-situ gel system for sustained ocular drug delivery. J Drug Targeting 2010;18:499â€“505.
14. De Campos AM, Sanchez A, Alonso MaJ. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface application to cyclosporine A. Int J Pharm 2001;224:159â€“68.
15. Calvo P, Vila-Jato JL, Alonso MaJ. Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers. Int J Pharm 1997;153:41â€“50.
16. Genta I, Conti B, Perugini P, Pavanetto F, Spadaro A, Puglisi G. Bioadhesive microspheres for ophthalmic administration of acyclovir. J Pharm Pharmacol 1997;49:737â€“42.
17. Dyer AM, Hinchcliffe M, Watts P. Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 2002;19(7):998-1008.
18. Illum L, Watts P, Fisher AN. Intranasal delivery of morphine. J Pharmacol Exp Ther 2002;301(1):391-400.
19. Bayat A, B Larijani, S Ahmadian, HE Junginger, M Rafiee-Tehrani. Preparation and characterization of insulin nanoparticles using chitosan and its quaternized derivatives. Nanomed: Nanotechnol Biol Med 2008;4(2):115-20.
20. Fisher A, Watling M, Smith A, Knight A. Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin, chitosan and chitosanâ€“poloxamer 188. Int J Clin Pharmacol Ther 2010;48:138â€“45.
21. Ana Portero, DesireÂ´e Teijeiro-Osorio, Maria J Alonso, Carmen RemunËœaÂ´n-LoÂ´pez. Development of chitosan sponges for buccal administration of insulin. Carbohydr Polym 2007;68:617â€“25.
22. Senel S, Ikinci G, Kas S. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 2000;193(2):197-203.
23. Giunchedi P, Juliano C, Gavini E. Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres. Eur J Pharm Biopharm 2002;53(2):233-9.
24. Remunan-Lopez C, Portero A, Vila-Jato JL, Alonso MJ. Design and evaluation of chitosan/ethylcellulose mucoadhesive bilayered devices for buccal drug delivery. J Controlled Release 1998;55:143-52.
25. N Langoth, H Kahlbacher, G SchÃ¶ffmann, I Schmerold, M Schuh, S Franz, et al. Bernkop-SchnÃ¼rch, Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system. Pharm Res 2006;23:573â€“9.
26. Bernkop-SchnÃ¼rch A, Walker G. Multifunctional matrices for oral peptide delivery. Crit Rev Ther Drug Carrier Syst 2001;18(5):459-501.
27. Thanou M, Verhoef JC, Junginger HE. Oral drug absorption enhancement by chitosan and its derivatives. Adv Drug Deliv Rev 2001;52(2):117-26.
28. Chandy T, Sharma CP. Chitosan matrix for oral sustained delivery of ampicillin. Biomater 1993;14(12):939-4.
29. Miyazaki S, Nakayama A, Oda M. Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery. Biol Pharm Bull 1994;17(5):745-7.
30. M Thanou, BI Florea, MWE LangemeÃ¿er, JC Verhoef, HE Junginger. N-trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (caco-2 cells) and in vivo (rats). Pharm Res 2000;17:27â€“31.
31. Hejazi R, Amiji M. Chitosan-based gastrointestinal delivery systems. J Controlled Release 2003;89:151â€“65.
32. Aiedeh K, Taha MO. Synthesis of chitosan succinate and chitosan phthalate and their evaluation as suggested matrices in orally administered, colon-specific drug delivery systems. Arch Pharm (Weinheim) 1999;332(3):103-7.
33. Lorenzo-Lamosa ML, C Remunan-Lopez, JL Vila-Jato, MJ Alonso. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Controlled Release 1998;52:109-18.
34. Surajit Das, Anumita Chaudhury, Ka-Yun Ng. Preparation and evaluation of zincâ€“pectinâ€“chitosan composite particles for drug delivery to the colon: Role of chitosan in modifying in vitro and in vivo drug release. Int J Pharm 2011;406:11â€“20.
35. Kawadkar J, A Ram. Colon targeted chitosan microsphere compressed matrices for the treatment of ulcerative colitis. Pharm inf Net 2007;5(4).
36. Tozaki H, Komoike J, Tada C. Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J Pharm Sci 1997;86(9):1016-21.
37. Zhang H, Alsarra IA, Neau SH. An in vitro evaluation of a chitosan-containing multiparticulate system for macromolecule delivery to the colon. Int J Pharm 2002;239(1-2):197-205.
38. Knapczyk J. Chitosan hydrogels as a base for semisolid drug forms. Int J Pharm 1993;93:233-7.
39. Gavini E, Sanna V, Juliano C, Bonferoni MC, Giunchedi P. Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug acriflavine. AAPS Pharm Sci Tech 2002;3:E20.
40. Bonferoni MC, Giunchedi P, Scalia S, Rossi S, Sandri G, Caramella C. Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms. AAPS Pharm Sci Tech 2006;7:5.
41. Kast CE, Valenta C, Leopold M. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Controlled Release 2002;81:347-54.
42. A El-Kamel, M Sokar, V Naggar, S Al Gamal. Chitosan and sodium alginate based bioadhesive vaginal tablets. AAPS J 2002;4:224â€“30.
43. G Sandri, S Rossi, F Ferrari, MC Bonferoni, C Muzzarelli, C Caramella. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci 2004;21:351â€“9.
44. D Raafat, H-G Sahl. Chitosan and its antimicrobial potentialâ€“a critical literature survey. Microb Biotechnol 2009;2:186â€“201.
45. Shimoda J, Onishi H, Machida Y. Bioadhesive characteristics of chitosan microspheres to the mucosa of rat small intestine. Drug Dev Ind Pharm 2001;27:567â€“76.
46. He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm 1998;166:75â€“88.
47. Park Y, Lee Y, Lee J, Seol C, Lee S. Controlled release of platelet-derived growth factor-BB from chondroitin sulfate-chitosan sponge for guided bone regeneration. J Controlled Release 2000;67:385-94.
48. Ramanathan S, Block L. The use of chitosan gels as matrices for electrically modulated drug delivery. J Controlled Release 2001;70:109-23.
49. Dodane V, Vilivalam VD. Pharmaceutical applications of chitosan. Pharm Sci Tech Today 1998;1:246â€“53.
50. Holme H, Hagen A, Dornish M. Influence of chitosan on permeability of human intestinal epithelial (Caco-2) cell: the effect of molecular weight and degree of deacetylation and exposure time. Adv Chitin Sci 2000;4:259-65.
51. Varshosaz J, F Jaffari, S Karimzadeh. Development of bioadhesive chitosan gels for topical delivery of lidocaine. Sci Pharm 2006;74:209-23.
52. Perugini P, Genta I, Pavanetto F. Study on glycolic acid delivery by liposomes and microspheres. Int J Pharm 2000;196(1):51-61.
53. D Thacharodi, K Panduranga Rao. Propranolol hydrochloride release behavior of cross linked chitosan membrane. J Chem Technol Biotechnol 1993;58:177.
54. D Thacharodi, K Panduranga Rao. Release of nifedipine through cross linked chitosan membranes. Int J Pharm 1993;96:33.
55. D Thacharodi, K Panduranga Rao. Development and in vitro evaluation of chitosan based transdermal drug delivery systems for controlled delivery of Propranolol hydrochloride. Biomater 1995;16:145.
56. Moes AJ. Gastro retentive dosage forms. Crit Rev Ther Drug Carrier Syst 1993;10:143-95.
57. Yang L, Eshraghi J, Fassihi R. A new intragastric delivery system for the treatment of helicobacter pylori associated gastric ulcer: in vitro evaluation. J Controlled Release 1999;57(3):215-22.
58. CE Kast, C Valenta, M Leopold, A Bernkop-SchnÃ¼rch. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Controlled Release 2002;81:347-54.
59. Prabaharan M, Mano JF. Chitosan-based particles as controlled drug delivery systems. Drug Delivery 2005;12(1):41-57.
60. Alexakis T, Boadi DK, Quong D. Microencapsulation of DNA within alginate microspheres and cross-linked chitosan membranes for in vivo application. Appl Biochem Biotechnol 1995;50(1):93-106.
61. Erbacher P, Zou S, Bettinger T, Steffan AM, Remy JS. Chitosan-based vector DNA complexes for gene delivery: Biophysical characteristics and transfection ability. Pharm Res 1998;15:1332-9.
62. Roy K, Mao HQ, Huang SK, Leong KW. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med 1999 5:387-91.
63. Shirui Mao, Wei Sun, Thomas Kissel. Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Delivery Rev 2010;62:12â€“27.
64. Kiang T, Wen J, Lim HW, Kam KW, Leong W. The effect of the degree of chitosan deacetylation on the efficiency of gene transfection. Biomaterials 2004;25(22):5293-301.
65. Sailaja AK, Amareshwar P, Chakravarty P. Chitosan nanoparticles as a drug delivery system. Res J Pharm Biol Chem Sci 2010;1(3):474-84.
66. Nydert P, Dragomir A, Hjelte L. Chitosan as a carrier for non-viral gene transfer in a cystic-fibrosis cell line. Biotechnol Appl Biochem 2008:51(4):153-7.
67. Germershaus O, Mao S, Sitterberg J, Bakowsky U, Kissel T. Gene delivery using chitosan, trimethyl chitosan or polyethylenglycol-graft-trimethyl chitosan block copolymers: establishment of structure-activity relationships in vitro. J Controlled Release 2008;125(2):145-54.
68. Kim YH, Gihm SH, Park CR, Lee KY, Kim TW, Kwon IC, et al. Structural characteristics of size-controlled self-aggregate of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier. Bioconjugate Chem 2001;12(6):932-8.
69. Jiang HL, Kim YK, Lee SM, Park MR, Kim EM, Jin YM, et al. Galactosylated chitosan-g-PEI/DNA complexes-loaded poly(organophosphazene) hydrogel as a hepatocyte targeting gene delivery system. Arch Pharm Res 2010;33(4):551-6.
70. Wang X, Yao J, Zhou JP, Lu Y, Wang W. Synthesis and evaluation of chitosan-graft-polyethylenimine as a gene vector. Pharmazie 2010;65(8):572-9.
71. Zhao X, Yin L, Ding J, Tang C, Gu S, Yin C, et al. Thiolated trimethyl chitosan nanocomplexes as gene carriers with high in vitro and in vivo transfection efficiency. J Controlled Release 2010;144(1):46-54.
72. Van der Lubben IM, Verhoef JC, Borchard G, Junginger HE. Chitosan for mucosal vaccination. Adv Drug Deliv Rev 2001;52:139-44.
73. Van der Lubben IM, Kersten G, Fretz MM, Beuvery C, Coos Verhoef J. Junginger HE. Vaccine 2003;21(13-14):1400-8.
74. Bacon A, Makin J, Sizer PJ, Jabbal-Gill I, Hinchcliffe M, Illum L. Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 2000;68:5764-70.
75. Xu W, Shen Y, Jiang Z, Wang Y, Chu Y, Xiong S. Intranasal delivery of chitosan-DNA vaccine generates mucosal SIgA and anti-CVB3 protection. Vaccine 2004;22(27â€“28):3603-12.
76. Bivas-Benita M, Laloup M, Versteyhe S, Dewit J, De Braekeleer J, Jongert E. Generation of Toxoplasma gondii GRA1 protein and DNA vaccine loaded chitosan particles: preparation, characterization, and preliminary in vivo studies. Int J Pharm 2003;266(1-2):17-27.
77. Xie Y, Zhou NJ, Gong YF, Chen J, Zhou XJ, Lu NH, et al. The immune response induced by H. pylori therapeutic vaccine with chitosan as adjuvant. J Gastroenterol Hepatol 2007;22:A239.
78. Hasegawa H, Ichinoche T, Tamura S, Kurata T. Development of mucosal vaccine for influenza viruses: preparation for a potential influenza pandemic. Expert Rev Vaccines 2007;6(2):193-201.
79. Slutter B, Jiskoot W. Dual role of CpG as immune modulator and physical crosslinker in ovalbumin loaded N-trimethyl chitosan (TMC) nanoparticles for nasal vaccination. J Controlled Release 2010;148:117â€“21.
80. Borges O, Cordeiro-da-Silva A, Romeijn SG. Uptake studies in rat Peyer's patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination. J Controlled Release 2006;114(3):348-58.
81. Jain S, Sharma RK, Vyas SP. Chitosan nanoparticles encapsulated vesicular systems for oral immunization: preparation, in-vitro and in-vivo characterization. J Pharm Pharmacol 2006;58(3):303-310.
82. Van der Lubben IM, Verhoef JC, Van Aelst A, Borchard G, Junginger HE. Chitosan microparticles for oral vaccination: preparation, characterization and preliminary in vivo uptake studies in murine peyerâ€™s patches. Biomaterials 2001;22:687.
83. Van der Lubben IM, Konings FAJ, Borchard G, Verhoef JC, Junginger HE. In vivo uptake of chitosan microparticles by murine peyerâ€™s patches: visualization studies using confocal laser scanning and immuno-histochemistry. J Drug Target 2001;9:39-47.
84. Struszczyk MH. Chitin and chitosan part II. Applications of chitosan. Polimery 2002;47:396-403.
85. Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci 2006;31:603-32.