title: In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits.
abstract: To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20-50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development.
authors.affiliation: Department of Mechanical Engineering, University of Texas at Tyler, Tyler TX, 75799, USA.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Chou
authors.affiliation: Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
authors.forename: Li-Jyuan
authors.initials: LJ
authors.lastname: Luo
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Biomedical Engineering Research Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC.|Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC.|Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan, ROC.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000737:chemistry*; D019781:Corneal Topography; D065546:Drug Liberation; D004596:Electroretinography; D005707:Gallic Acid / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D005782:Gels / Q000737:chemistry*; D005901:Glaucoma / Q000188:drug therapy*; D010862:Pilocarpine / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D012160:Retina / Q000473:pathology; D013696:Temperature
chemical_list: D000975:Antioxidants; D001672:Biocompatible Materials; D005782:Gels; D010862:Pilocarpine; D005707:Gallic Acid; D005780:Gelatin