Pharmaceutical applications of chitosan

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Abstract

Considerable research efforts have been directed towards the development of safe and efficient chitosan-based drug delivery systems. In this review, the authors outline the major new approaches to the pharmaceutical applications of chitosan and discuss its mechanisms of action in various in vitro and in vivo models.

Section snippets

Oral drug delivery

The bioavailability of drugs has been improved by the use of mucoadhesive dosage forms[19]. By prolonging the residence time of drug carriers at the absorption site, sustained release and improved bioavailability of drugs can be achieved. It is acknowledged that chitosan possesses good mucoadhesive properties, as demonstrated in vitro by Lehr et al.[20], who observed that chitosan performed better when compared with hydroxypropylcellulose and carboxymethylcellulose. Among chitosans of various

Chitosan in gel systems

Unique delivery systems have been developed for a controlled and targeted delivery of active compounds. One approach taken by Hoffman et al.[64]was to synthesize hybrid copolymers by grafting temperature-responsive polymers (Pluronic®) to chitosan backbones. The polymers gelled as the temperature was raised from 4°C to 37°C and provided significant extension of drug release. The bioadhesive character of chitosan on mucosal surfaces prolonged the residence time of the formulation on such

Safety of chitosan

As stated in the introduction, chitosan is a collective term applied to deacetylated chitins in various stages of deacetylation and depolymerization. Almost all functional properties of chitosan depend on the chain length, charge density and charge distribution. Numerous studies have demonstrated that the salt-form20, 24, 60, 71, molecular weight20, 72, degree of deacetylation30, 72as well as the pH at which chitosan is used[73]influence the properties of this polymer in drug delivery systems.

Mechanisms of action of chitosan

As described throughout this review, chitosan is being studied extensively as an enhancer for transmucosal drug delivery in vitro and in vivo. However, there is still much to be accomplished in understanding its mechanisms of action on mucosal epithelium. These studies would help in optimizing the type and amount of chitosan used in pharmaceutical applications. The mechanism of action of chitosan was suggested to be a combination of mucoadhesion and an effect on tight-junction (TJ) regulation

Conclusions

Outstanding scientific progress has been made, demonstrating the application of chitosan in drug delivery systems. As stated in the introduction, the properties of chitosan make it a versatile excipient, not only for controlled release applications but also as a bioadhesive polymer, depending on the route of delivery. In addition, it appears to have potential as an absorption enhancer promoting drug uptake across the mucosal barrier. To date, the lack of an approved product containing chitosan

Acknowledgements

We gratefully acknowledge the members of the Cell Biology group, both past and present, who contributed to some of the results reported in this review. We would also like to thank D. Morel, M. Amin Khan, and J.R. Merwin for their critical review of the manuscript. The help of L. Lewis in the aquisition of some of the references was greatly appreciated.

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