Chitosan as Carrier for Topical Ocular Drug Delivery (I)

Bacterial keratitis is a serious ocular infectious disease that can lead to significant vision loss. The common treatment regimen for bacterial keratitis is frequent administration of topical ocular antibacterial agents. However, the use of frequent dosing may result in toxicity. The success of an antibacterial therapy depends on features of the antibiotic, such as its antimicrobial spectrum and potency, as well as on the ophthalmic vehicle. Ideally, an ophthalmic formulation that increases the contact time with the ocular surface should allow therapeutic levels to be maintained over a prolonged period of time. Another problem is that ocular drug delivery is extremely hampered by the defensive barriers of the corneal epithelial cell layers. Thus, the efficacy of a topically administered drug delivery system depends on interaction with the ocular mucosa, protection from degradation, and facilitation of delivery to the ocular tissues. Since mucoadhesive polymer can increase the residence time of drugs on the ocular surface, the cationic polymer chitosan, possesses some favorable biological characteristics such as biodegradability, nontoxicity, and biocompatibility that make it a promising candidate for ocular drug delivery. Traditionally, the problems associated with powerful eye drop treatment can be minimized through the use of disposable soft contact lenses for ophthalmic drug delivery. The contact lenses are soaked in the drug solution but they can only provide drug delivery for a few hours. In an attempt to improve the drawbacks mentioned above, we propose a new concept to immobilize chitosan on the surface of contact lenses for development of topical ocular drug delivery system. In this study, the chitosan-immobilized contact lenses were prepared using a carbodiimide-mediated coupling reaction. The electrostatic interactions between oppositely charged substances allow the ofloxacin to bind to chitosan molecules, forming polyion complexes. In the first year of this project, the effect of molecular weight and deacetylation degree of chitosan on the functionality of drug carriers was investigated. In the second year of this project, the chitosan-modified carriers for topical ocular delivery of ofloxacin were examined in a rabbit model. It is expected that the proposed controlled-release technique in this project will be beneficial in helping people who are experiencing vision loss.

Project ID:PB9709-3572
External Project ID:NSC97-2221-E182-003