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

Carbohydrate Polymers
Li-Jyuan LuoMichiya Matsusaki

Abstract

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.

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Citations

Oct 27, 2018·International Journal of Molecular Sciences·Jui-Yang LaiDavid Hui-Kang Ma
Mar 12, 2020·Polymers·Tatiana S DeminaTatiana A Akopova
Dec 31, 2020·Polymers·Ines CazinSandra Schlögl
Apr 12, 2020·International Journal of Biological Macromolecules·Raelle F GomesRegina C M de Paula
Dec 10, 2021·Macromolecular Bioscience·Zuhan ChenYanfeng Wang

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