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Li-Jyuan Luo, Jui-Yang Lai; Development of injectable antioxidant drug carriers for glaucoma therapy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6112. doi: https://doi.org/.
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Clinically, the oxidative stress has been considered as an initiating factor of ocular hypertention, thereby causing glaucomatous tissue damages. In order to enable a dual-function mechanism to effectively treat glaucomatous oxidative injury and intraocular pressure (IOP) dysregulation, the antioxidant molecules are chemically grafted onto drug carriers to facilitate the development of new pharmacological treatment strategies.
Biodegradable in situ gelling gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were functionalized with different antioxidant molecules such as gallic acid (GA) and eudesmic acid (EA) by redox radical initiation reaction. The delivery performance, antioxidant activity, and ocular biocompatibility of polymeric carrier materials were evaluated. In this study, the animal use protocols were approved by the Institutional Animal Care and Use Committee of Chang Gung University and were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The ocular hypertension-induced retinal and optic nerve tissue morphologies were examined.
Although both studied groups exhibited similar pilocarpine release profiles, the GNGA carriers exhibited stronger antioxidant action than their GNEA counterparts. Ocular cell line cultures exposed to these polymeric gel depots showed normal morphological characteristics and metabolic activities, indicating good biocompatibility. In the pilocarpine/GNGA groups, sustained therapeutic drug concentrations in aqueous humor are achieved, which is important in protection against corneal aberration and retinal injury. In contrast, after intracameral administration of drug-containing GNEA, insufficient level of pilocarpine for IOP reduction is detected. The antioxidant GA-functionalized injectable hydrogels are found to significantly contribute to enhancement of retinal antioxidant defense system and preservation of optic nerve histological structure at 2 weeks postoperatively.
The present study highlights the benefits of appropriate antioxidant biodegradable thermogels to prevent glaucoma development.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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