title: Evaluation of an injectable thermosensitive hydrogel as drug delivery implant for ocular glaucoma surgery.
abstract: In this study, a biodegradable thermo-sensitive hydrogel from poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (PTMC15-F127-PTMC15) was designed and evaluated as an injectable implant during ocular glaucoma filtration surgery in vivo and in vitro. Mitomycin C (MMC) was loaded into this hydrogel for controlled released to prolong the efficacy and to reduce the long-term toxicity. The properties of the hydrogel were confirmed using 1H NMR and gel permeation chromatography (GPC). Compared to the Pluronic F127 hydrogel, the PTMC15-F127-PTMC15 hydrogel showed a good solution-gel transition temperature at 37°C, a lower work concentration of 5% w/v and a longer mass loss time of more than 2 weeks. The in vitro study showed that the drug could be released from PTMC15-F127-PTMC15 (5% w/v) hydrogel for up to 16 days with only 57% of drug released in the first day. Moreover, the cell toxicity, which was tested via LDH and ANNEXIN V/PI, decreased within 72 h in human tenon's fibroblast cells (HTFs). The in vivo behavior in a rabbit glaucoma filtration surgery model indicated that this hydrogel loaded with 0.1 mg/ml MMC led to a better functional bleb with a prolonged mean bleb survival time (25.5±2.9 days). The scar tissue formation, new collagen deposition and myofibroblast generation appeared to be reduced upon histological and immunohistochemistry examinations, with no obvious side effects and inflammatory reactions. The in vitro and in vivo results demonstrated that this novel hydrogel is a safe and effective drug delivery candidate in ocular glaucoma surgery.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xi
authors.affiliation: DSAPM and PCFM Lab, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: DSAPM and PCFM Lab, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Qiongjuan
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, PR China; Aier Eye Hospital Group, Changsha, Hunan, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Second Xiang Ya Hospital, Central south university, Changsha, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Yale Eye Center, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.affiliation: DSAPM and PCFM Lab, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Daping
authors.initials: D
authors.lastname: Quan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004343:Drug Implants; D018463:Filtering Surgery / Q000379:methods*; D005901:Glaucoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D016685:Mitomycin / Q000008:administration & dosage; D011817:Rabbits
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D016685:Mitomycin