Peck K D, Hsu J, Li S K, Ghanem A H, Higuchi W I
Department of Pharmaceutics and Pharmaceutical Chemistry, 301 Skaggs Hall, University of Utah, Salt Lake City, Utah 84112, USA.
J Pharm Sci. 1998 Sep;87(9):1161-9. doi: 10.1021/js970012r.
This study focused upon the enhancement effects of ionic surfactants upon passive and electroosmotic transdermal flux. The first phase of the study involved validating theories relating surface properties of a membrane to electroosmotic solvent flow under appropriate experimental conditions using a synthetic model membrane (stack of 50 Nuclepore membranes). Numerical solutions to the Poisson-Boltzmann equation and the equations of fluid motion served as the theoretical basis for the experimental studies. Important outcomes of the model membrane studies were that electroosmotic solvent flow velocity was enhanced by the addition of an anionic surfactant, sodium dodecyl sulfate, and reversed by the addition of a cationic surfactant, dodecyltrimethylammonium bromide. The effective membrane pore wall surface charge densities were determined under a variety of experimental conditions. Adsorption of dodecyl sulfate to the pore wall increased the net negative charge on the pore wall. A reversal of the net pore wall surface charge density resulted from the adsorption of dodecyltrimethylammonium. The interrelationship between electroosmosis, surfactant adsorption, and ionic strength was also evaluated. The second phase of the study was an investigation of the effects of sodium dodecyl sulfate upon the transport of neutral polar permeants through human epidermal membrane (HEM). Fluxes of [14C]urea and [3H]sucrose were simultaneously measured across HEM samples under passive and 250 mV conditions; flux measurements were made before, during, and after HEM exposure to sodium dodecyl sulfate. A systematic analysis of the experimental data made it possible to elucidate the specific contributions of sodium dodecyl sulfate and the applied electric potential to the overall flux enhancement. Sodium dodecyl sulfate enhanced the intrinsic passive permeability of the HEM, and it also enhanced the contribution of electroosmosis to the flux during iontophoresis.
本研究聚焦于离子型表面活性剂对被动和电渗皮肤通量的增强作用。研究的第一阶段涉及在适当的实验条件下，使用合成模型膜（50层核孔膜堆叠）验证与膜表面性质和电渗溶剂流动相关的理论。泊松-玻尔兹曼方程和流体运动方程的数值解作为实验研究的理论基础。模型膜研究的重要结果是，添加阴离子表面活性剂十二烷基硫酸钠可提高电渗溶剂流速，而添加阳离子表面活性剂十二烷基三甲基溴化铵则使其逆转。在各种实验条件下测定了有效膜孔壁表面电荷密度。十二烷基硫酸根吸附到孔壁上增加了孔壁上的净负电荷。十二烷基三甲基铵的吸附导致孔壁表面净电荷密度的逆转。还评估了电渗、表面活性剂吸附和离子强度之间的相互关系。研究的第二阶段是调查十二烷基硫酸钠对中性极性渗透剂通过人表皮膜（HEM）转运的影响。在被动和250 mV条件下，同时测量[14C]尿素和[3H]蔗糖在HEM样品上的通量；在HEM暴露于十二烷基硫酸钠之前、期间和之后进行通量测量。对实验数据的系统分析使得阐明十二烷基硫酸钠和施加的电势对整体通量增强的具体贡献成为可能。十二烷基硫酸钠提高了HEM的固有被动通透性，并且在离子电渗过程中也增强了电渗对通量的贡献。
