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经巩膜被动和离子导入传输:理论与分析。

Transscleral passive and iontophoretic transport: theory and analysis.

机构信息

a Division of Pharmaceutical Sciences, James L Winkle College of Pharmacy , University of Cincinnati , Cincinnati , OH , USA.

b Department of Pharmaceutical Science and Research, School of Pharmacy , Marshall University , Huntington , WV , USA.

出版信息

Expert Opin Drug Deliv. 2018 Mar;15(3):283-299. doi: 10.1080/17425247.2018.1406918. Epub 2017 Dec 5.

Abstract

INTRODUCTION

The sclera is considered the 'static barrier,' a main barrier for transscleral drug delivery. The characterization of passive and iontophoretic transport across the sclera in vitro is the first step toward our ability to predict transscleral drug delivery. Although previous studies have investigated this topic, the quantitative structure permeation relationships (QSPR) for passive and iontophoretic transscleral transport are not available.

AREAS COVERED

This review evaluated previous results of transscleral passive and iontophoretic transport in vitro and examined QSPR for transscleral permeation of small permeants and macromolecules. Passive permeation data in the literature were compared with respective to the animal species employed in the studies. Data variability was investigated. Electrotransport theory and the mechanisms of iontophoresis were reviewed and used to analyze the iontophoresis data.

EXPERT OPINION

QSPR was examined for passive transscleral permeation, showing correlations between logarithm of permeability coefficient and logarithm of molecular weight. Potential causes of data variability were proposed. QSPR were established for electroosmosis using the molecular weight of neutral permeants and for iontophoresis enhancement using the molecular weight and charge of ionic permeants. However, QSPR for charged macromolecules were empirical; iontophoretic flux enhancement was significantly smaller than Nernst-Planck model prediction due to complicating factors.

摘要

简介

巩膜被认为是“静态屏障”,是经巩膜药物递送的主要屏障。体外研究巩膜的被动和离子电渗传输特性是我们能够预测经巩膜药物递送的第一步。尽管先前的研究已经探讨了这个课题,但目前还没有关于被动和离子电渗经巩膜转运的定量构效关系(QSPR)。

涵盖领域

本综述评估了先前关于小渗透物和大分子经巩膜被动和离子电渗体外转运的研究结果,并考察了经巩膜渗透的 QSPR。文献中的被动渗透数据与研究中使用的动物物种进行了比较。研究了数据变异性。综述了电迁移理论和离子电渗的机制,并用于分析离子电渗数据。

专家意见

对被动经巩膜渗透进行了 QSPR 研究,结果表明渗透率系数的对数与分子量的对数之间存在相关性。提出了数据变异性的潜在原因。使用中性渗透物的分子量建立了电渗流的 QSPR,使用离子渗透物的分子量和电荷建立了离子电渗增强的 QSPR。然而,带电荷的大分子的 QSPR 是经验性的;由于复杂因素,离子电渗通量的增强明显小于 Nernst-Planck 模型的预测。

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