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关于眨眼对基于聚甲基丙烯酸羟乙酯水凝胶药物释放的影响:一项体外研究。

About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro study.

作者信息

Galante R, Paradiso P, Moutinho M G, Fernandes A I, Mata J L G, Matos A P A, Colaço R, Saramago B, Serro A P

机构信息

a Centro de Química Estrutural, Instituto Superior Técnico , Universidade de Lisboa , Av. Rovisco Pais, 1049-001 Lisboa , Portugal.

出版信息

J Biomater Sci Polym Ed. 2015;26(4):235-51. doi: 10.1080/09205063.2014.994948. Epub 2015 Jan 2.

Abstract

The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug-loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before. Two poly-2-hydroxyethylmethacrylate-based hydrogels, pHEMA-T and pHEMA-UV, were used as model materials. Levofloxaxin was chosen as model drug. The hydrogels were fully characterized in what concerns structural and physicochemical properties. pHEMA-UV revealed some superficial porosity and a lower short-range order than pHEMA-T. We observe that the load and friction cycles enhanced the drug release from pHEMA-UV hydrogels. The application of a simple mathematical model, which takes into account the drug dilution caused by the tear flow, showed that the enhancement of the drug release caused by blinking on this hydrogel may be relevant in in vivo conditions. Conversely, the more sustained drug release from pHEMA-T is not affected by load and friction cycles. The conclusion is that, depending on the physicochemical and microstructural characteristics of the hydrogels, blinking is a factor that may affect the amount of drug delivered to the eye by SCLs and should thus be considered.

摘要

近年来,能够延长药物在眼内停留时间并提高其相对于眼药水的生物利用度的新型眼科给药系统的开发一直是深入研究的对象。多项研究表明,载药治疗性软性隐形眼镜(SCL)是一种很有前景的方法,与眼药水相比具有几个潜在优势。这项工作的主要目的是研究由眨眼引起的重复负载和摩擦循环对用于SCL的水凝胶药物释放的影响,据我们所知,此前从未对此进行过研究。两种基于聚甲基丙烯酸2-羟乙酯的水凝胶pHEMA-T和pHEMA-UV被用作模型材料。左氧氟沙星被选为模型药物。对水凝胶的结构和物理化学性质进行了全面表征。pHEMA-UV显示出一些表面孔隙率,且短程有序性低于pHEMA-T。我们观察到负载和摩擦循环增强了pHEMA-UV水凝胶的药物释放。应用一个考虑泪液流动引起的药物稀释的简单数学模型表明,眨眼对这种水凝胶药物释放的增强作用在体内条件下可能具有相关性。相反,pHEMA-T更持续的药物释放不受负载和摩擦循环的影响。结论是,根据水凝胶的物理化学和微观结构特征,眨眼是一个可能影响SCL输送到眼内药物量的因素,因此应该予以考虑。

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