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

Li Jyuan Luo, Chih Ching Huang, Hung Chi Chen, Jui Yang Lai*, Michiya Matsusaki

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)375-384
Number of pages10
JournalCarbohydrate Polymers
Volume197
DOIs
StatePublished - 01 10 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Ltd

Keywords

  • Biodegradable thermogels
  • Chitosan-g-poly(N-isopropylacrylamide)
  • Controlled pilocarpine release
  • Deacetylation degree
  • Injectable drug carrier

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