Pharmaceutical Applications of Chitosan

Following is a detailed account of the areas in which chitosan, as a drug carrier and a pharmaceutical aid, has been successfully explored. 

Route of administration Formulation system Drug incorporated Property imparted by chitosan to the delivery system Reference 

Oral Microspheres Amoxycillin, Metronidazole Gastroretentive drug delivery [57] [58] 

Buccal Tablets containing drug loaded chitosan microspheres Chlorohexidine Prolonged release of the drug in buccal cavity [87] 

Ophthalmic Microspheres Acyclovir Prolonged release of drug and enhancement of ocular bioavailabihty [89] 

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Dodane, V., and V.D. Vilivalam. 1998. Pharmaceutical applications of chitosan. Pharm Sci Technol Today 1 246. 

Most of the early biomedical and pharmaceutical application of chitosan-based systems dealt with topical applications and a few controlled drug... 

Dermal drug administration is yet another pharmaceutical application of chitosan. Topical all-frans-retinoic acid (ATRA) is an effective treatment for serious malignant melanoma. However, this topical retinoid incites skin irritation in the wide majority of patients, rendering it an ineffective treat-ment. As evidenced by the research of Cattaneo and Demierre, chitosan gels avail themselves to sustained, topical release of ATRA. These studies showed that manipulation of the viscosity or chitosan concentration of the gel enabled control of percutaneous penetration of the drug in mouse skin samples. In addition, their clinical trials on healthy hiunan subjects indicated minimal erythema occurrence from application of 0.1% ATRA in 1% and 3% chitosan gel. 

Sawayanagi et al. [301] reported the fluidity and compressibility of combined powders, viz., lactose/chitin, lactose/chitosan, potato starch/chitin, potato starch/chitosan as well as the disintegration properties of tablets made from these powders in comparison with those of combined powders of lactose/MCC and potato starch/MCC. This was done in order to develop direct compression dilutents as a part of their studies on pharmaceutical applications of chitin and chitosan. 

Recent research explored various chemically modified conjugates and derivatives to improve its physico-chemical and biological properties. This modification allows significant applications of chitosan in various disciplines of biomedical research. So far various fabrication methods have been employed for the development of chemically modified chitosan e.g. chitosan-poly(acrylic acid) nanoparticles and acylated chitosan nanoparticles have been recently explored to examine their modifications effect on physicochemical properties and blood compatibility [151, 152], Similarly self-aggregated NPs of cholesterol-modified 0-carboxymethyl chitosan conjugates were fabricated to improve the pharmaceutical and biomedical applications of chitosan [153], Various examples of chitosan and its chemically modified synthetic derivatives are mentioned in Table 3.2. 

PEGylation is an excellent approach to modify the properties of biomaterials and to explore their diverse applications in biomedical science [193]. Various pegylated biomaterials especially PEGylated chitosan derivatives with their significant applications are reported e.g. Casettari et al. explored synthesis, characterizations and pharmaceutical applications of PEGylated chitosan derivatives [193]. Similarly Zhu et al. demonstrated the synthesis and characterization of PEG modified N-trimethylaminoethyhnethacrylate chitosan nanoparticles [194]. 

Figure 2.2 An overview of applicability of chitosan in pharmaceutical technology.

Table 9.3 Some examples of the recent applications of chitosan in the formulation of microspheres and nanoparticles for several pharmaceutical applications.

Chitosan, produced commercially by deacetylation of chitin, is a natural polysaccharide composed of randomly distributed (J-l, 4-linked D-glucosamine and N-acetyl-a-glucosamine. Because of its nontoxic, biocompatible, biodegradable and mucoadhesive properties, chitosan is widely used in the pharmaceutical field [171]. Chitosan has been used as a carrier system for hormones [172], proteins [173], enzymes [174], and genes [175]. Because of its apparent pKa = 5.6 [176], the application of chitosan in the oral administration of protein and peptide drugs is restricted by its easy dissolution in a low pH environment. 

Another way to achieve desirable polymer properties is the modification of preformed polymers. This modification may take place on the reactive sites of the polymer chain through alkylation, hydrolysis, sulfonation, esterification, and other various reactions of polymers. Examples of natural polymers and their modifications are cellulose and its derivatives, chitin and chitosan, and polysaccharides. These are still to this day very important polymers for pharmaceutical applications. 

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