Ophthalmic delivery of cyclosporine A by punctal plugs
Ophthalmic delivery of cyclosporine A by punctal plugs
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DOI：
10.1016/j.jconrel.2010.11.009
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发表时间：
2011-02-28
影响因子：
10.8
通讯作者：
Chauhan, Anuj
中科院分区：
文献类型：
--
作者：
Gupta, Chhavi;Chauhan, Anuj
干眼的治疗方法是滴入环孢霉素A乳剂滴眼液或在泪小管中插入泪点塞以阻塞泪液引流。本文重点介绍了一种新的方法，开发的泪点塞，也可以释放环孢素A，以提供一个双重机制治疗干眼症。泪点塞由一个圆柱形的甲基丙烯酸羟乙酯核心含有药物微粒包围的不渗透的硅外壳，覆盖约50%的核心，与未覆盖的部分直接对眼睛。这种设计的几何形状与专利文献中的那些明显不同，专利文献中的那些大多数设计成棒状。塞以约3 μ g/天的速率以零级释放环孢霉素A约3个月。预期体内释放速率约为该值的一半。一个数学模型，提供了一个准确的估计释放没有任何拟合参数。还开发了通过Restasis和泪点塞递送药物的药代动力学模型，并且基于这些模型，约1.5 μ g/天的释放速率可能是治疗有效的。眼部药代动力学模型的预测与人类报告的测量结果合理一致。(C)2010爱思唯尔有限公司版权所有。
Dry eyes are treated by instillation of eye drops of cyclosporine A emulsion or by punctal plug insertion in canaliculus to block tear drainage. This paper focuses on a novel approach of developing a punctal plug that can also release cyclosporine A to provide a dual mechanism for treating dry eyes.The punctal plug consists of a cylindrical hydroxy ethyl methacrylate core containing drug microparticles surrounded by an impermeable silicone shell that covers about 50% of the core, with the uncovered part directed towards the eyes. The geometry of this design is significantly different from those in patent literature, which are mostly designed to be rods.Plugs release cyclosporine A for a period of about 3 months at zero-order at a rate of about 3 mu g/day. The in vivo release rates are expected to be about half of this value. A mathematical model is presented that provides an accurate estimate of the release without any fitting parameter. Pharmacokinetic models are also developed for drug delivered through Restasis (R) and punctal plugs, and based on these models the release rate of about 1.5 mu g/day may be therapeutically effective. The predictions of the ocular pharmacokinetic model are in reasonable agreement with reported measurements in humans. (C) 2010 Elsevier B.V. All rights reserved.