离子交换膜增强经巩膜离子电渗转运

Enhanced transscleral lontophoretic transport with ion-exchange membrane.

作者信息

Li S Kevin, Zhu Honggang, Higuchi William I

机构信息

Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.

出版信息

Pharm Res. 2006 Aug;23(8):1857-67. doi: 10.1007/s11095-006-9010-9.

DOI:10.1007/s11095-006-9010-9

PMID:16841198

Abstract

PURPOSE

Transscleral iontophoresis has been recently re-examined for drug delivery to the back of the eye. In conventional iontophoresis, due to the relatively high electromobility of the endogenous competing ions (counterions) relative to that of the drug ion in the tissue barrier, the efficiency of iontophoretic drug delivery is generally low. The objective of the present study was to examine ion-exchange membrane-enhanced transscleral iontophoretic transport in which the ion-exchange membrane in series with the sclera can hinder the transport of the competing counterions and selectively allow the transport of the permeant across the sclera.

METHODS

The physical properties of the Ionac ion-exchange membrane and excised rabbit sclera were determined in equilibrium uptake experiments and in passive and iontophoretic transport experiments with salicylate, tetraethylammonium, urea, and mannitol. Transscleral experiments with the ion-exchange membrane were conducted with salicylate and excised rabbit sclera in vitro. The contribution of electroosmosis to electrotransport during transscleral iontophoresis was assessed with urea and mannitol.

RESULTS

The ion-exchange membrane is highly positively charged and has a small effective pore size. The sclera is relatively porous with a large effective pore size and low pore tortuosity. The sclera is also net negatively charged but this does not significantly affect the transport of small ions. A three-fold steady-state transscleral flux enhancement of salicylate was observed in ion-exchange membrane-enhanced iontophoresis over conventional transscleral iontophoresis without the membrane. Such enhancement was relatively independent of the applied electric current density and the thickness of the studied ion-exchange membrane assembly. Although the ion-exchange membrane altered transscleral electroosmosis, the contribution of electroosmosis to electrotransport was not significant.

CONCLUSIONS

The present study has demonstrated the potential of ion-exchange membranes for enhancing iontophoretic transport and drug delivery.

摘要

目的

经巩膜离子电渗疗法最近被重新研究用于向眼后部递送药物。在传统的离子电渗疗法中，由于内源性竞争离子（抗衡离子）在组织屏障中的电迁移率相对于药物离子较高，离子电渗药物递送的效率通常较低。本研究的目的是研究离子交换膜增强的经巩膜离子电渗转运，其中与巩膜串联的离子交换膜可以阻碍竞争抗衡离子的转运，并选择性地允许渗透物穿过巩膜。

方法

在平衡摄取实验以及水杨酸、四乙铵、尿素和甘露醇的被动及离子电渗转运实验中，测定了Ionac离子交换膜和切除的兔巩膜的物理性质。使用离子交换膜对水杨酸和切除的兔巩膜进行了体外经巩膜实验。用尿素和甘露醇评估了经巩膜离子电渗疗法期间电渗对电转运的贡献。

结果

离子交换膜带高度正电荷，有效孔径较小。巩膜相对多孔，有效孔径大且孔曲折度低。巩膜也带净负电荷，但这对小离子的转运没有显著影响。与没有膜的传统经巩膜离子电渗疗法相比，在离子交换膜增强的离子电渗疗法中观察到水杨酸的稳态经巩膜通量提高了三倍。这种增强相对独立于所施加的电流密度和所研究的离子交换膜组件的厚度。尽管离子交换膜改变了经巩膜电渗，但电渗对电转运的贡献并不显著。