Vanbever R, Prausnitz M R, Préat V
Unité de Pharmacie galénique, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium.
Pharm Res. 1997 May;14(5):638-44. doi: 10.1023/a:1012161313701.
Macromolecules were investigated as chemical enhancers of transdermal transport by skin electroporation. Although unable to enhance passive or iontophoretic transport, macromolecules are proposed to enhance electroporation-assisted delivery by stabilizing the increased permeability caused by high-voltage pulses.
To test this hypothesis, we examined the timescale of transport, the influence of electrical protocol and the influence of macromolecule size, structure, and charge on enhancement of transdermal mannitol transport in vitro by heparin, dextran-sulfate, neutral dextran, and poly-lysine.
Skin electroporation increased transdermal mannitol delivery by approximately two orders of magnitude. The addition of macromolecules further increased transport up to five-fold, in support of the proposed hypothesis. Macromolecules present during pulsing enhanced mannitol transport after pulsing for hours, apparently by a macromolecule-skin interaction. No enhancement was observed during passive diffusion or low-voltage iontophoresis, suggesting that macromolecules interact specifically with transport pathways created at high voltage. Although all macromolecules studied enhanced transport, those with greater charge and size were more effective.
This study demonstrates that macromolecules can be used as transdermal transport enhancers uniquely suited to skin electroporation.
研究大分子作为皮肤电穿孔介导的经皮转运化学增强剂的作用。尽管大分子不能增强被动或离子电渗转运，但有人提出它们可通过稳定高压脉冲引起的通透性增加来增强电穿孔辅助递送。
为验证这一假设，我们研究了转运的时间尺度、电参数的影响以及大分子的大小、结构和电荷对肝素、硫酸葡聚糖、中性葡聚糖和聚赖氨酸在体外增强经皮甘露醇转运的影响。
皮肤电穿孔使经皮甘露醇递送增加了约两个数量级。添加大分子进一步使转运增加了五倍，支持了所提出的假设。脉冲期间存在的大分子在脉冲数小时后增强了甘露醇转运，显然是通过大分子与皮肤的相互作用。在被动扩散或低电压离子电渗过程中未观察到增强作用，这表明大分子与高压下形成的转运途径特异性相互作用。尽管所研究的所有大分子都增强了转运，但电荷和尺寸较大的大分子更有效。
本研究表明，大分子可作为特别适用于皮肤电穿孔的经皮转运增强剂。
