title: Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis.
abstract: The formation of a scar after glaucoma surgery often leads to unsuccessful control of intraocular pressure, and should be prevented by using a variety of methods. We designed and developed a novel drug delivery system (DDS) comprising cyclosporine A (CsA) and poly(lactic-co-glycolic acid) (PLGA) based on a glaucoma drainage device (GDD) that can continuously release CsA to prevent postoperative fibrosis following glaucoma surgery. The CsA@PLGA@GDD DDS was observed by field emission scanning electron microscopy and revealed an asymmetric pore structure. Thermogravimetric analysis was performed to measure the weight loss and evaluate the thermal stability of the CsA@PLGA@GDD DDS. The in vitro drug release profile of the DDS was studied using high performance liquid chromatography, which confirmed that the DDS released CsA at a stable rate and maintained adequate CsA concentrations for a relatively long time. The biocompatibility of the DDS and the inhibitory effects on the postoperative fibrosis were investigated in vitro using rabbit Tenon's fibroblasts. The in vivo safety and efficacy of the DDS were examined by implanting the DDS into Tenon's capsules in New Zealand rabbits. Bleb morphology, intraocular pressure, anterior chamber reactions, and anterior chamber angiography were studied at a series of set times. The DDS kept the filtration pathway unblocked for a longer time compared with the control GDD. The results indicate that the CsA@PLGA@GDD DDS represents a safe and effective strategy for preventing scar formation after glaucoma surgery.
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China.
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China.
authors.forename: Jiaxu
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Research Center, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China; State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200031, China. Electronic address: sjgsun@126.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China. Electronic address: xhsun@shmu.edu.cn.
authors.forename: Xinghuai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D004322:Drainage / Q000295:instrumentation; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005123:Eye / Q000098:blood supply / Q000000981:diagnostic imaging; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control*; D005451:Fluorescein Angiography; D005901:Glaucoma / Q000473:pathology; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D013818:Thermogravimetry
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine
keywords: Cyclosporine A (CsA); Drug delivery system (DDS); Glaucoma drainage device (GDD); Poly(lactic-co-glycolic acid)(PLGA); Postoperative fibrosis