Chemical Engineering Department, University of Florida, Gainesville, FL 32611-6005, USA.
J Control Release. 2011 Feb 28;150(1):70-6. doi: 10.1016/j.jconrel.2010.11.009. Epub 2010 Nov 11.
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 μg/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® and punctal plugs, and based on these models the release rate of about 1.5 μg/day may be therapeutically effective. The predictions of the ocular pharmacokinetic model are in reasonable agreement with reported measurements in humans.
干眼症可通过滴注环孢素 A 乳剂或在泪小管中插入泪点塞来阻止泪液引流进行治疗。本文介绍了一种开发泪点塞的新方法，该塞还可以释放环孢素 A，为干眼症的治疗提供双重机制。泪点塞由圆柱形羟乙基甲基丙烯酸酯芯组成，其中包含药物微球，被不渗透的硅壳覆盖，约占芯的 50%，未被覆盖的部分朝向眼睛。这种设计的几何形状与专利文献中的那些有很大的不同，后者大多设计为棒状。塞子以零级速度约每天 3μg 释放约 3 个月的环孢素 A。体内释放率预计约为该值的一半。本文提出了一个数学模型，该模型无需任何拟合参数即可准确估计释放情况。还开发了通过 Restasis®和泪点塞输送药物的药代动力学模型，并基于这些模型，每天约 1.5μg 的释放速度可能具有治疗效果。眼部药代动力学模型的预测与在人体中报告的测量值基本一致。
