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Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentally- induced dry eye syndrome

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Nano Research 2015年第2期8卷 621-635页

作者： Shengyan Liu Chu Ning Chang Mohit S. Verma Denise Hileeto Alex Muntz Ulrike Stahl Jill Woods lyndonw. jones Frank X. Gu Department of Chemical Engineering University of Waterloo Waterloo N2L 3G1 Canada Waterloo Institute for Nanotechnology University of Waterloo Waterloo N2L3G1 Canada Centre for Contact Lens Research University of Waterloo Waterloo N2L3G1 Canada

Topical formulations, commonly applied for treatment of anterior eye diseases, require frequent administration due to rapid clearance from the ocular surface, typically through the lacrimal drainage system or through over-spillage onto the lids. We report on a mucoadhesive nanoparticle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The nanoparticles were formed from self-assembly of block copolymers composed of poly（D, L-lactide） and Dextran. The enhanced mucoadhesion properties were achieved by surface functionalizing the nanoparticles with phenylboronic acid. The nanoparticles encapsulated up to 12 wt.% of Cyclosporine A （CycA） and sustained the release for up to five days at a clinically relevant dose, which led us to explore the therapeutic efficacy of the formulation with reduced administration frequency. By administering CycA-loaded nanoparticles to dry eye-induced mice once a week, inflammatory infiltrates were eliminated and the ocular surface completely recovered. The same once a week dosage of the nanoparticles also showed no signs of physical irritation or inflammatory responses in acute （1 week） and chronic （12 weeks） studies in healthy rabbit eyes. These findings indicate that the nanoparticles may significantly reduce the frequency of administration for effective treatment of anterior eye diseases without causing ocular irritation.

关键词： biocompatibility copolymer mucoadhesion nanoparticle drug delivery ophthalmology

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