Abstract
Chitosan, obtained by deacetylation of chitin, is a natural, hydrophilic, nontoxic, biocompatible, and biodegradable polysaccharide suitable for applications in pharmaceutical technology. Its role in drug delivery systems was examined by considering the chemical and biologic properties of the polymer.
Chitosan is a nonbranched homopolymer formed by β-(1,4)-linked glucosamine units; hydroxyls and the amino groups are substrates for chemical modifications aimed at obtaining suitable materials for different purposes.
Chitosan is soluble at acidic pH, forming gels; hydrogels are also formed in the presence of negatively charged drugs or polyanions, and represent a sustained drug release form. The bioadhesive nature of chitosan can be attributed to the same type of ionic interactions with mucosal membrane components. Mucoadhesive formulations have been developed for ocular, nasal, buccal, gastrointestinal, and vaginal drug administration. Chitosan is able to promote transmucosal absorption of small polar drugs, including peptides, inducing a transient opening of the tight junctions of the cell membrane.
Due to its polymeric nature, chitosan has been widely investigated for a variety of microparticulate pharmaceutical forms. Chitosan is also a candidate for potential applications in the delivery of radiopharmaceuticals, genes and peptides.
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References
Ravi Kumar MNV. A review of chitin and chitosan applications. React Funct Poly 2002; 46: 1–27
Shepherd R, Reader S, Falshaw A. Chitosan functional properties. Glycoconj J 1997; 14:535–42
Skaugrud O. Chitosan: new biopolymer for cosmetics and drugs. Drug Cosmetic Ind 1991; 148: 24–9
Cartier N, Domard A, Chanzy H. Single crystals of chitosan. Int J Biol Macromol 1990; 12: 289–94
Rege PR, Shukla DJ, Block LH. Chitinosans as tableting excipients for modified release delivery system. Int J Pharm 1999; 181: 49–60
Paul W, Sharma CP. Chitosan, a drug carrier for the 21st century: a review. STP Pharma Sci 2000; 10: 5–22
Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm Res 1998; 15(9): 1326–31
Singla AK, Chawla M. Chitosan: some pharmaceutical and biological aspects: an update. J Pharm Pharmacol 2001; 53(8): 1047–67
Felt O, Buri P, Gurny R. Chitosan: a unique polysaccharide for drug delivery. Drug Dev Ind Pharm 1998; 24: 979–93
Akbuga J. A biopolymer: chitosan. Int J Pharm Adv 1995; 1: 1–18
Machida Y, Nagai T. Chitin/chitosan as pharmaceutical excipients. In: Breimer DD, Crommelin DJA, Midha KK, editors. Topic in pharmaceutical sciences 1989: proceedings of the 49th International Congress of Pharmaceutical Sciences; FIP, 1989: Munich: 211–21
Muzzarelli RAA, editor. Natural chelating polymers. New York: Pergamon Press, 1973
Muzzarelli RAA, Muzzarelli C, editors. Chitosan in pharmacy and chemistry. Italy: Arec, 2002
Sabnis S, Block LH. Chitosan as an enabling excipient for drug delivery systems (I): molecular modifications. Int J Biol Macromol 2000; 27: 181–6
Tomihata K, Ikada Y. In vitro and in vivo degradation of films of chitin and its de-acetylated derivatives. Biomaterials 1997; 18(7): 567–75
Chatelet C, Damour O, Domard A. Influence of the degree of acetylation on some biological properties of chitosan films. Biomaterials 2001; 22(3): 261–8
Allan GG, Peyron M. Molecular weight manipulation of chitosan (I): kinetics of de-polymerization by nitrous acid. Carbohydr Res 1995; 277(2): 257–72
Pochanavanich P, Suntornsuk W. Fungal chitosan production and its characterization. Lett Appl Microbiol 2002; 35(1): 17–21
Kawada J, Yui T, Okuyama K, et al. Crystalline behavior of chitosan organic acid salts. Biosci Biotechnol Biochem 2001; 65: 2542–7
Leffler CC, Müller BW. Influence of the acid type on the physical and drug liberation properties of chitosan-gelatin sponges. Int J Pharm 2000; 194: 229–37
Errington N, Harding SE, Varum KM, et al. Hydrodynamic characterisation of chitosan varying in molecular weight and degree of acetylation. Int J Biol Macromol 1993; 15: 113–7
Thanou MM, Kotze AF, Scharringhausen T, et al. Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal caco-2 cell monolayers. J Control Release 2000; 64(1–3): 15–25
Mariappan MR, Alas EA, Williams JG, et al. Chitosan and chitosan sulfate have opposing effects on collagen-fibroblast interactions. Wound Repair Regen 1999; 7(5): 400–6
Sano H, Shibasaki K, Matsukubo T, et al. Comparison of the activity of four chitosan derivatives in reducing initial adherence of oral bacteria onto tooth surfaces. Bull Tokyo Dent Coll 2001; 42(4): 243–9
Machida Y, Nagai T, Abe M, et al. Use of chitosan and hydroxypropylchitosan in drug formulations to effect sustained release. Drug Des Deliv 1986; 1(2): 119–30
Philippova OE, Volkov EV, Sitnikova NL, et al. Two types of hydrophobic aggregates in aqueous solutions of chitosan and its hydrophobic derivative. Biomacromolecules 2001; 2(2): 483–90
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
Bernkop-Schnürch A. Chitosan and its derivatives: potential excipients for peroral peptide delivery systems. Int J Pharm 2000; 194(1): 1–13
Cardenas G, Orlando P, Edelio T. Synthesis and applications of chitosan mercaptanes as heavy metal retention agent. Int J Biol Macromol 2001; 28(2): 167–74
Sawayanagy Y, Nambu N, Nagai T. Directly compressed tablets containing chitin or chitosan in addition to lactose or potato starch. Chem Pharm Bull (Tokyo) 1982; 30: 2935–40
Ilango R, Kavimani S, Premila J, et al. Studies on tablets of sulfamethoxazole using chitosan. Indian J Pharm Sci 1997; 59: 229–4
Sabnis SS, Rege PR, Block LH. Use of chitosan in compressed tablets of diclofenac sodium: inhibition of drug release in an acidic environment. Pharm Dev Technol 1997; 2(3): 243–55
Dodane V, Vilivalam VD. Pharmaceutical applications of chitosan. Pharm Sci Technol Today 1998; 1(6): 246–53
Ilango R, Jayakar B, Kavimani S. Chitosan as a new pharmaceutical excipient. East Pharmacist 1998; 41: 47–9
Upadrashta SM, Katikaneni PR, Nuessle NO. Chitosan as tablet binder. Drug Dev Ind Pharm 1992; 18: 1701–8
Nagai T, Sawayanagi Y, Nambu N. Application of chitin and chitosan to pharmaceutical preparations. In: Zikakis JP, editor. Chitin, chitosan and related enzymes. Orlando (FL): Academic Press Inc, 1984: 21–40
Ritthidej GC, Chomto P, Pummangura S, et al. Chitin and chitosan as disintegrants in paracetamol tablets. Drug Dev Ind Pharm 1992; 18: 1701–8
Nigalaye AG, Adusumili P, Bolton S. Investigation of prolonged drug release from matrix formulations of chitosan. Drug Dev Ind Pharm 1990; 16: 449–67
Mi FL, Her NL, Kaun CY, et al. Chitosan tablets for controlled drug release of theophylline: effect of polymer drug wet or dry blending and anionic-cationic interpolymer. J Appl Polym Sci 1997; 66: 2495–9
Sawayanagi Y, Nambu N, Nagai T. Enhancement of dissolution properties of griseofulvin from ground mixture with chitin and chitosan. Chem Pharm Bull (Tokyo) 1982; 30: 4464–7
Portero A, Remuñan-Lopez C, Vila-Jato JL. Effect of chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int J Pharm 1998; 175: 75–84
Soane RJ, Frier M, Perkins AC, et al. Evaluation of the clearance characteristics of bioadhesive systems in human. Int J Pharm 1999; 178: 55–65
He P, Davis SS, Illum L. In vitro evaluation of mucoadhesive properties of chitosan microspheres. Int J Pharm 1988; 166: 75–88
Hassan EE, Gallo JM. A simple rheological method for the in vitro assessment of mucin polymer bioadhesive bond strength. Pharm Res 1990; 7: 491–5
Takayama K, Hirata M, Machida Y, et al. Effect of interpolymer complex formation on bioadhesive property and drug release phenomenon of compressed tablets consisting of chitosan and sodium hyaluronate. Chem Pharm Bull 1990; 38(7): 1993–7
Lehr C-M, Boustra JA, Schacht EH, et al. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 1992; 78: 43–8
Takeuchi H, Yamamoto H, Niwa T, et al. Enterai absorption of insulin in rats from mucoadhesive chitosan-coated liposomes. Pharm Res 1996; 13(6): 896–901
Illum L, Farraj NF, Davis SS. Chitosan as a novel nasal delivery system for peptides drugs. Pharm Res 1994; 11(8): 1186–9
Thanou M, Verhoef JC, Junginger HE. Oral drug absorption enhancement by chitosan and its derivatives. Adv Drug Deliv Rev 2001; 52(2): 117–26
Thanou M, Verhoef JC, Junginger HE. Chitosan and its derivatives, as intestinal absorption enhancer. Adv Drug Deliv Rev 2001; 50Suppl. 1: S91–101
Aungst BJ, Saitoh H, Burcham DL, et al. Enhancement of the intestinal absorptions of peptides and non-peptides. J Control Release 1996; 41: 19–31
Schipper NG, Olsson S, Hoogstraate JA, et al. Chitosans as absorption enhancers for poorly absorbable drugs (2): mechanism of absorption enhancement. Pharm Res 1997; 14(7): 923–9
Dodane V, Khan MA, Merwin JR. Effect of chitosan on epithelial permeability and structure. Int J Pharm 1999; 182(1): 21–32
Schipper NGM, Varum KM, Stenberg P, et al. Chitosans as absorption enhancers of poorly absorbable drugs (3): influence of mucus on absorption enhancement. Eur J Pharm Sci 1999; 8: 335–43
Ilango R, Kavimani S, Jaykar B, et al. Dissolution studies on tablets of ibuprofen using chitosan. Indian J Exp Biol 1999; 37(5): 505–8
Acartürk F. Preparation of a prolonged-release tablet formulation of diclofenac sodium (part I): using chitosan. Pharmazie 1989; 44(8): 547–9
Miyazaki S, Nakayama A, Oda M, et al. Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery. Biol Pharm Bull 1994; 17(5): 745–7
Aiedeh K, Orienti I, Bertasi V, et al. Chitosan and chitosan linked to triethylene glycol glutarate or betain as tabletting excipients for the sustained release of indomethacin. STP Pharma Sci 1998; 8(5): 291–6
Blau S, Jubeh TT, Haupt SM, et al. Drug targeting by surface cationization. Crit Rev Ther Drug Carrier Syst 2000; 17(5): 425–65
Lorenzo-Lamosa ML, Remuñan-Lopez C, Vila-Jato JL, et al. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Control Release 1998; 52(1–2): 109–18
Puttipipatkhachorn S, Nunthanid J, Yamamoto K, et al. Drug physical state and drug-polymer interaction on drug release from chitosan matrix films. J Control Release 2001; 75(1–2): 143–53
Gallaher CM, Munion J, Hesslink Jr R, et al. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr 2000; 130(11): 2753–9
Sugano M, Fujikawa T, Hiratsuyi Y, et al. A novel use of chitosan as a hypocholesterolemic agent in rats. Am J Clin Nutr 1980; 33: 787–93
Draget KI, Varum KM, Moen E, et al. Chitosan cross-linked with Mo (VI) polyoxyanions: a new gelling system. Biomaterials 1992; 13(9): 635–8
Denuziere A, Ferrier D, Damour O, et al. Chitosan-chondroitin sulfate and chitosan-hyaluronate polyelectrolyte complexes: biological properties. Biomaterials 1998; 19(14): 1275–85
Chenite A, Chaput C, Wang D, et al. Novel injectable neutral solution of chitosan from biodegradable gels in situ. Biomaterials 2000; 21: 2155–61
Miyazaki S, Ishii K, Nadai T. The use of chitin and chitosan as drug carrier. Chem Pharm Bull (Tokyo) 1981; 29: 3067–9
Tasker RA, Connell BJ, Ross SJ, et al. Development of an injectable sustainedrelease formulation of morphine: antinociceptive properties in rats. Lab Anim 1998; 32(3): 270–5
Knapczyk J. Chitosan hydrogel as a base for semisolid drug forms. Int J Pharm 1993; 93: 233–7
Hou WM, Miyazaki S, Takada M, et al. Sustained release of indomethacin from chitosan granules. Chem Pharm Bull 1985; 33: 3986–92
Risbud MV, Bhonde RR. Polyacrylamide-chitosan hydrogels: in vitro biocompatibility and sustained release studies. Drug Deliv 2000; 7(2): 69–75
Mitra S, Gaur U, Ghosh PC, et al. Tumor targeted delivery of encapsulated dextrandoxorubicin conjugate using chitosan nanoparticles as carrier. J Control Release 2001; 74(1–3): 317–23
Noble L, Gray AI, Sadiq L, et al. A non-covalently cross-linked chitosan based hydrogel. Int J Pharm 1999; 192(2): 173–82
Jeong B, Kim SW, Bae YH. Thermosensitive sol-gel reversible hydrogels. Adv Drug Del Rev 2002; 54: 37–51
Uchegbu IF, Schatzlein AG, Tetley L, et al. Polymeric chitosan-based vesicles for drug delivery. J Pharm Pharmacol 1998; 50(5): 453–8
Miekka SI, Jameson T, Singh M, et al. Novel delivery systems for coagulation proteins. Haemophilia 1998; 4(4): 436–42
Kost J, Langer R. Responsive polymeric delivery systems. Adv Drug Deliv Rev 2001; 46(1–3): 125–48
Janes KA, Calvo P, Alonso MJ. Polysaccharide colloidal particles as delivery system for macromolecules. Adv Drug Deliv Rev 2001; 47(1): 83–97
Yoshioka H, Nonaka K-I, Fukuda K, et al. Chitosan-derived polymer surfactants and their micellar properties. Biosci Biotechnol Biochem 1995; 59(10): 1901–4
Miwa A, Ishibe A, Nakano M, et al. Development of novel chitosan derivatives as micellar carriers of taxol. Pharm Res 1998; 15(12): 1844–50
Kim YK, Gihm SH, Park CR. Structural characteristics of size-controlled self-aggregates of deoxycholic acid modified chitosan and their application as a DNA delivery carrier. Bioconjug Chem 2001; 12: 932–8
Kas HS. Chitosan: properties, preparations and applications to microparticulate systems. J Microencapsul 1997; 14(6): 689–711
Muzzarelli R, Baldassarre V, Conti F, et al. Biological activity of chitosan: ultra-structural study. Biomaterials 1998; 9: 247–52
Mooren FC, Berthold A, Domschke W, et al. Influence of chitosan microspheres on the transport of prednisolone sodium phosphate across HT-29 cell monolayers. Pharm Res 1998; 15(1): 58–65
Nascimento A, Laranjeira MC, Favere VT, et al. Impregnation and release of aspirin from chitosan/poly (acrylic acid) graft copolymer microspheres. J Microencapsul 2001; 18(5): 679–84
Stolberg J, Laranjeira MC, Sanchez MN, et al. Microspheres of chitosan/poly (vinylalcohol) incorporating tetrasulphonated copper (II) phthalocyanine: preparation and characterization. J Microencapsul 1999; 16(4): 431–8
Hejazi R, Amiji M. Stomach-specific anti-H. pylori therapy (I): preparation and characterization of tetracyline-loaded chitosan microspheres. Int J Pharm 2002; 235(1–2): 87–94
Sezer AD, Akbuga J. Release characteristics of chitosan treated alginate beads (II): sustained release of a low molecular drug from chitosan treated alginate beads. J Microencapsul 1999; 16(6): 687–96
Sezer AD, Akbuga J. Release characteristics of chitosan treated alginate beads (I): sustained release of a macromolecular drug from chitosan treated alginate beads. J Microencapsul 1999; 16(2): 195–203
Vandenberg GW, De La Noüe J. Evaluation of protein release from chitosanalginate microcapsules produced using external or internal gelation. J Microencapsul 2001; 18(4): 433–41
Lim ST, Martin GP, Berry DJ, et al. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release 2000; 66: 281–92
Fernandez UR, Calvo P, Remunan-Lopez C, et al. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm Res 1999; 16(10): 1576–81
Shu XZ, Zhu KJ. Chitosan/gelation microspheres prepared by modified emulsification and ionotropic gelation. J Microencapsul 2001; 18(2): 237–45
Ma Z, Yeoh HH, Lim LY. Formulation pH modulates the interaction of insulin with chitosan nanoparticles. J Pharm Sci 2002; 91(6): 1396–404
Dyer AM, Hinchcliffe M, Watts P, et al. 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
De Campos AM, Sanchez A, Alonso MJ. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface: application to cyclosporin A. Int J Pharm 2001; 224: 159–68
Shu XZ, Zhu KJ. A novel approach to prepare tripolyphosphate/chitosan complex beads for controlled release drug delivery. Int J Pharm 2000; 201: 51–8
Janes KA, Fresneau MP, Marazuela A, et al. Chitosan nanoparticles as delivery systems for doxorubicin. J Control Release 2001; 73(2–3): 255–67
Mi FL, Tan Y-C, Liang H-F, et al. In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant. Biomaterials 2002; 23(1): 181–91
Aiedeh K, Gianasi E, Orienti I, et al. Chitosan microcapsules as controlled release systems for insulin. J Microencapsul 1997; 14: 567–76
He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying. Int J Pharm 1999; 187(1): 53–65
Ganza Gonzalez A, Anguiano-Igea S, Otero-Espinar FJ, et al. Chitosan and chondroitin microspheres for oral-administration controlled release of metoclopramide. Eur J Pharm Biopharm 1999; 48(2): 149–55
Perugini P, Genta I, Pavanetto F, et al. Study on glycolic acid delivery by liposomes and microspheres. Int J Pharm 2000; 196(1): 51–61
Giunchedi P, Juliano C, Gavini E, et al. Formulation and in vivo evaluation of Chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres. Eur J Pharm Biopharm 2002; 53(2): 233–9
He P, Davis SS, Illum L. Sustained release chitosan microspheres prepared by novel spray drying methods. J Microencapsul 1999; 16(3): 343–55
Genta I, Perugini P, Pavanetto F, et al. Microparticulate drug delivery systems. EXS 1999; 87: 305–13
Kaur IP, Smitha R. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev Ind Pharm 2002; 28(4): 353–69
Felt O, Furrer P, Mayer JM, et al. Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention. Int J Pharm 1999; 180(2): 185–93
Felt O, Baeyens V, Buri P, et al. Delivery of antibiotics to the eye using a positively charged polysaccharide as vehicle. AAPS PharmSci 2001; 3(4): E34
Genta I, Conti B, Perugini P, et al. Bioadhesive microspheres for ophthalmic administration of acyclovir. J Pharm Pharmacol 1997; 49(8): 737–42
Davis SS. Delivery of peptide and non-peptide drugs through the respiratory tract. Pharm Sci Technol Today 1999; 2(11): 450–6
Illum L, Watts P, Fisher AN, et al. Intranasal delivery of morphine. J Pharmacol Exp Ther 2002; 301(1): 391–400
Hinchcliffe M, Illum L. Intranasal insulin delivery and therapy. Adv Drug Deliv Rev 1999; 35: 199–234
Vila A, Sanchez A, Tobio M, et al. Design of biodegradable particles for protein delivery. J Control Release 2002; 78(1–3): 15–24
Lim ST, Forbes B, Berry DJ, et al. In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits. Int J Pharm 2002; 231(1): 73–82
Needleman IG, Smales FC. In vitro assessment of bioadhesion for periodontal and buccal drug delivery. Biomaterials 1995; 16(8): 617–24
Needleman I, Mather SJ, Martin GP, et al. Periodontal pocket clearance by gamma scintigraphy in human volunteers. J Clin Periodontol 2000; 27(12): 904–9
Senel S, Ikinci G, Kas S, et al. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 2000; 193(2): 197–203
Senel S, Kremer MJ, Kas S, et al. Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials 2000; 21(20): 2067–71
Senel S, Hincal AA. Drug permeation enhancement via buccal route: possibilities and limitations. J Control Release 2001; 72(1–3): 133–44
Bernkop-Schnürch A, Walker G. Multifunctional matrices for oral peptide delivery. Crit Rev Ther Drug Carrier Syst 2001; 18(5): 459–501
Chandy T, Sharma CP. Chitosan matrix for oral sustained delivery of ampicillin. Biomaterials 1993; 14(12): 939–4
Sinha VR, Kumria R. Polysaccharides in colon-specific drug delivery. Int J Pharm 2001; 224(1–2): 19–38
Sinha VR, Kumria R. Binders for colon specific drug delivery: an in vitro evaluation. Int J Pharm 2002; 249(1–2): 23–31
Tozaki H, Odoriba T, Okada N, et al. Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats. J Control Release 2002; 82(1): 51–61
Orienti I, Cerchiara T, Luppi B, et al. Influence of different chitosan salts on the release of sodium diclofenac in colon-specific delivery. Int J Pharm 2002; 238(1–2): 51–9
González-Rodríguez ML, Holgado MA, Sánchez-Lafuente C, et al. Alginate/chitosan particulate systems for sodium diclofenac release. Int J Pharm 2002; 232: 225–34
Tozaki H, Komoike J, Tada C, et al. Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J Pharm Sci 1997; 86(9): 1016–21
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
Zhang H, Neau SH. In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonie contents. Biomaterials 2002; 23(13): 2761–6
Macleod GS, Fell JT, Collett JH, et al. Selective drug delivery to the colon using pectin: chitosan: hydroxypropyl methyl cellulose film coated tablets. Int J Pharm 1999; 187(2): 251–7
Shimono N, Takatori T, Ueda M, et al. Chitosan dispersed system for colon-specific drug delivery. Int J Pharm 2002; 245(1–2): 45–54
Kast CE, Valenta C, Leopold M, et al. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Control Release 2002; 81: 347–54
Thacharodi D, Rao KP. Development and in vitro evaluation of chitosan-based transdermal drug delivery systems for the controlled delivery of propranolol hydrochloride. Biomaterials 1995; 16(2): 145–8
Wang YY, Hong CT, Chiu WT, et al. In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels. Int J Pharm 2001; 224(1–2): 89–104
Fang JY, Leu YL, Wang YY, et al. In vitro topical application and in vivo pharmacodynamic evaluation of nonivamide hydrogels using Wistar rat as an animal model. Eur J Pharm Sci 2002; 15(5): 417–23
Tsai CJ, Hsu LR, Fang JY, et al. Chitosan hydrogel as a base for transdermal delivery of berberine and its evaluation in rat skin. Biol Pharm Bull 1999; 22(4): 397–401
Hosoya O, Sano M, Wada Y, et al. Effect of several hydrophilic polymers on the permeation of morphine and salicylic acid through excised hairless rat skin. Chem Pharm Bull (Tokyo) 1998; 46(5): 882–5
Piron E, Domard A. Interactions between chitosan and alpha emitters: 238Pu and 241Am. Int J Biol Macromol 1998; 23(2): 121–5
Suzuki YS, Momose Y, Higashi N, et al. Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice. J Nucl Med 1998; 39(12): 2161–6
Song J, Suh CH, Park YB, et al. A phase I/IIa study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis. Eur J Nucl Med 2001; 28(4): 489–97
Shin BC, Park KB. Preparation of 153Sm-chitosan complex for radiation synovectomy. Nucl Med Biol 2001; 28(6): 719–25
Shikata F, Tokumitsu H, Ichikawa H, et al. In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer. Eur J Pharm Biopharm 2002; 53(1): 57–63
Borchard G. Chitosans for gene delivery. Adv Drug Deliv Rev 2001; 52: 145–50
Illum L, Jabbal-Gill I, Hinchcliffe M, et al. Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev 2001; 51: 81–96
Mao HQ, Roy K, Troung-Le VL, et al. Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release 2001; 70(3): 399–421
Kabbaj M, Phillips NC. Anticancer activity of mycobacterial DNA: effect of formulation as chitosan nanoparticles. J Drug Target 2001; 9(5): 317–28
Alexakis T, Boadi DK, Quong D, et al. Microencapsulation of DNA within alginate microspheres and cross-linked chitosan membranes for in vivo application. Appl Biochem Biotechnol 1995; 50(1): 93–106
van der Lubben IM, Verhoef JC, Borchard G, et al. Chitosan for mucosal vaccination. Adv Drug Deliv Rev 2001; 52(2): 139–44
van der Lubben IM, Verhoef JC, Borchard G, et al. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur J Pharm Sci 2001; 14(3): 201–7
MacLaughlin FC, Mumper RJ, Wang J, et al. Chitosan and depolymerized chitosan oligomers as condensing carriers for in vivo plasmid delivery. J Control Release 1998 Dec; 56(1–3): 259–72
Kast CE, Bernkop-Schnurch A. Thiolated polymers-thiomers: development and in vitro evaluation of chitosan-thioglycolic acid conjugates. Biomaterials 2001; 22(17): 2345–52
Bernkop-Schnürch A, Kast CE. Chemically modified chitosans as enzyme inhibitors. Adv Drug Deliv Rev 2001; 52(2): 127–37
Portera A, Remunan-Lopez C, Nielsen HM. The potential of chitosan in enhancing peptide and protein absorption across the TR146 cell culture model: an in vitro model of the buccal epithelium. Pharm Res 2002; 19(2): 169–74
Tengamnuay P, Sahamethapat A, Sailasuta A, et al. Chitosans as nasal absorption enhancers of peptides: comparison between free amine chitosans and soluble salts. Int J Pharm 2000; 197(1–2): 53–67
Onal S, Zihnioglu F. Encapsulation of insulin in chitosan-coated alginate beads: oral therapeutic peptide delivery. Artif Cells Blood Substit Immobil Biotechnol 2002; 30(3): 229–37
Kawashima Y, Yamamoto H, Takeuchi H, et al. Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm Dev Technol 2000; 5(1): 77–85
Arai K, Kinumaki T, Fujita T. Toxicity of chitosan. Bull Tokai Reg Fish Lab 1968; 43: 89–94
Acikgoz M, Kas HS, Hashelik Z, et al. Chitosan microspheres of diclofenac sodium (II): in vitro and in vivo evaluation. Pharmazie 1995; 50: 275–7
Rao SB, Sharma CP. Use of chitosan as a biomaterial: studies on its safety and haemostatic potential. J Biomed Mater Res 1997; 34: 21–8
Hirano S. Chitin and chitosan as novel biotechnological material. Polym Int 1999; 48: 732–8
Ravi Kumar MN. Nano and microparticles as controlled drug delivery devices. J Pharm Pharm Sci 2000; 3(2): 234–58
Kumar MN, Kumar N. Polymeric controlled drug-delivery systems: perspective issues and opportunities. Drug Dev Ind Pharm 2001; 27(1): 1–30
Gupta KC, Ravi Kumar MNV. Drug release behavior of beads and microgranules of chitosan. Biomaterial 2000; 21: 1115–9
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This work was supported by MURST (ex-40%) Funds, and Italy/Spain Integrated Action Funds.
The authors have provided no information on conflicts of interest that are directly relevant to the content of this review.
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Fini, A., Orienti, I. The Role of Chitosan in Drug Delivery. Am J Drug Deliv 1, 43–59 (2003). https://doi.org/10.2165/00137696-200301010-00004
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DOI: https://doi.org/10.2165/00137696-200301010-00004