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用于眼部药物递送的粘膜粘附性丙烯酰基季铵化聚甲基丙烯酸二甲氨基乙酯纳米凝胶的合成与评价

Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels for ocular drug delivery.

作者信息

Brannigan Ruairí P, Khutoryanskiy Vitaliy V

机构信息

School of Pharmacy, University of Reading, Reading, RG6 6UR, UK.

School of Pharmacy, University of Reading, Reading, RG6 6UR, UK.

出版信息

Colloids Surf B Biointerfaces. 2017 Jul 1;155:538-543. doi: 10.1016/j.colsurfb.2017.04.050. Epub 2017 Apr 27.

Abstract

Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via surfactant-free free-radical polymerization technique in aqueous conditions utilizing N,N'-methylene-bis-acrylamide (MBA) as a crosslinking agent. The PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to yield mucoadhesive materials which incorporate two mucoadhesive concepts; electrostatic interactions and covalent bond forming acrylate groups. The native PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo bovine conjunctival tissues, which was found to increase proportionally with the degree of quaternization. With a view to determine the ocular drug delivery capabilities of the materials, both quaternized and native nanogels were loaded with pilocarpine hydrochloride via an absorption method, and their in vitro release profiles were analysed. The nanogels were found to exhibit a high loading capacity (>20% of total weight) and a sustained release over 6h.

摘要

聚(甲基丙烯酸2-二甲基氨基乙酯)(PDMAEMA)纳米凝胶是在水相条件下,利用N,N'-亚甲基双丙烯酰胺(MBA)作为交联剂,通过无表面活性剂自由基聚合技术合成的。随后,PDMAEMA纳米凝胶用丙烯酰氯进行季铵化,以制备包含两种粘膜粘附概念的粘膜粘附材料;静电相互作用和形成共价键的丙烯酸酯基团。发现天然PDMAEMA纳米凝胶在离体牛结膜组织上表现出良好的粘膜粘附性能,并且发现其与季铵化程度成比例增加。为了确定材料的眼部给药能力,通过吸收法将季铵化和天然纳米凝胶都负载盐酸毛果芸香碱,并分析它们的体外释放曲线。发现纳米凝胶具有高负载量(>总重量的20%)并在6小时内持续释放。

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