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Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers

Luo, Li-Jyuan, Huang, Chih-Ching, Chen, Hung-Chi, Lai, Jui-Yang, Matsusaki, Michiya
Carbohydrate polymers 2018 v.197 pp. 375-384
DNA damage, biodegradability, biodegradation, caspase-3, cell culture, chitosan, composite polymers, cytotoxicity, drug carriers, epithelial cells, glaucoma, pilocarpine, rabbits
Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations. For the first time, this study investigates the effect of deacetylation degree (DD) of the polysaccharide component in chitosan-g-poly(N-isopropylacrylamide) (CN) carriers on controlled release of pilocarpine in the management of glaucoma. Our results showed that increasing the chitosan DD from 60.7% to 98.5% leads to enhanced biodegradation resistance of carrier and prolonged release profile of the drug. Significant DNA damage and caspase-3 activation could be detected in lens epithelial cell cultures exposed to CN made from highly deacetylated polysaccharides, indicating apoptosis-related cytotoxicity due to relatively high positive charge density of the graft copolymers. Postoperative outcomes demonstrated that long-term therapeutic efficacy in glaucomatous rabbits is governed by intraocular pressure changes in response to intracamerally administered pilocarpine-loaded CN, strongly suggesting the usefulness of deacetylation in this injectable drug delivery carrier.