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Long-acting drug delivery systems with advanced functionalities are critically important to pharmacologically treat glaucomatous optic neuropathy, a chronic and multifactorial neurodegenerative disease. Here, a novel strategy based on the methoxylation effects of benzoic acid derivatives was exploited to rationally design a biodegradable and injectable thermogel, which possesses potent antioxidant activities and sustained drug delivery abilities for treating glaucomatous nerve damage. In particular, 4-hydroxy-3,5-dimethoxybenzoic acid, consisting of two methoxyl groups and one hydroxyl group at the position para to the carboxylic group, was demonstrated to contribute to the strong antioxidant activities of a chitosan-g-poly(N-isopropylacrylamide) biomaterial while maintaining the drug encapsulation/release efficiencies of the thermogel. The pharmacological treatment relies on the intracameral injection of the thermogel coloaded with pilocarpine and RGFP966 and exhibits significant improvement in the attenuation of neurodegeneration via suppressing oxidative stress, lowering ocular hypertension, reducing retinal ganglion cell loss and enhancing myelin growth and neuron regeneration. These findings on the development of long-acting drug delivery systems with extended functions show great promise for the management of glaucoma-related neurodegeneration.
Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Full article11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)