title: Chitosan-g-poly(N-isopropylacrylamide) copolymers as delivery carriers for intracameral pilocarpine administration.
abstract: This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials. The increase in grafting ratio facilitated temperature triggered gelation and drug encapsulation at physiological conditions. Additionally, the slow biodegradation process of delivery carriers was responsible for the delayed pilocarpine release, which allowed that the drug concentration could reach minimum therapeutic level for treating glaucoma during 42days of the study. All of the synthesized Chi-PN carriers demonstrated good ocular biocompatibility with lens epithelial cell cultures. In a rabbit model of experimental glaucoma, the intraocular pressure-lowering and miotic as well as corneal endothelial preservation responses to pilocarpine strongly depended on the drug release profiles. It is concluded that injectable biodegradable chitosan-based thermogels can be potentially utilized as intracameral biomaterials for extended release of antiglaucoma medications and improved performance of delivery carriers.
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, Republic of China; Biomedical Engineering Research Center, Chang Gung University, Taoyuan 33302, Taiwan, Republic of China; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, Republic of China; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, Republic of China; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan, Republic of China. Electronic address: jylai@mail.cgu.edu.tw.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan, Republic of China.
authors.forename: Li-Jyuan
authors.initials: LJ
authors.lastname: Luo
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D060433:Administration, Ophthalmic; D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D010862:Pilocarpine / Q000008:administration & dosage*; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D018721:Muscarinic Agonists; D010862:Pilocarpine; C052970:poly-N-isopropylacrylamide; D048271:Chitosan
keywords: Chitosan; Delivery carrier; Intracameral pilocarpine administration; Poly(N-isopropylacrylamide)