Peck K D, Srinivasan V, Li S K, Higuchi W I, Ghanem A H
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84112, USA.
J Pharm Sci. 1996 Jul;85(7):781-8. doi: 10.1021/js950044j.
This study focused upon quantitatively determining the influence of permeant molecular size upon flux enhancement which results from electroosmosis. The first phase of the study involved validation of a fundamental model describing the molecular size dependence of flux enhancement which results from convective solvent flow. This was accomplished using a model synthetic membrane (stack of 50 Nuclepore membranes) and four model permeants with a molecular weight range of 60-504 (urea, mannitol, sucrose, and raffinose). The steady-state flux of each permeant was determined under passive conditions and applied voltages of 125, 250, 500, and 1000 mV using side-by-side diffusion cells and a four-electrode potentiostat system. On the basis of the permeability enhancement for each permeant at each applied voltage (relative to the passive permeability) it was possible to calculate the effective solvent flow velocity from each permeant at each field strength. An important finding was that the flux enhancement due to electroosmosis was strongly molecular weight dependent (i.e., the flux enhancement ratio was around 4 times greater for raffinose than for urea, with mannitol and sucrose yielding intermediate values), while the calculated effective flow velocity at each voltage was independent of the molecular weight of the permeant. This coupled with a linear correlation between flow velocity and applied voltage served to establish the validity of the method and model. The second phase of the study was an extension of the model to human epidermal membrane (HEM). These experiments involved simultaneously measuring the fluxes of [14C]urea and [3H]sucrose across HEM samples under passive, 250 mV, and 500 mV conditions. Similar to the Nuclepore system, the observed flux enhancement ratios with HEM were approximately 3 times greater for sucrose than for urea. A detailed analysis of the HEM data showed semiquantitative agreement between predictions of the model and experimental results.
本研究着重于定量测定渗透分子大小对电渗作用所导致的通量增强的影响。研究的第一阶段涉及验证一个描述对流溶剂流所导致的通量增强的分子大小依赖性的基础模型。这是通过使用一个模型合成膜（50 层核孔膜堆叠）和四种分子量范围为 60 - 504 的模型渗透物（尿素、甘露醇、蔗糖和棉子糖）来完成的。使用并排扩散池和四电极恒电位仪系统在被动条件以及 125、250、500 和 1000 mV 的施加电压下测定每种渗透物的稳态通量。基于每种渗透物在每个施加电压下的渗透率增强（相对于被动渗透率），可以计算出每种渗透物在每个场强下的有效溶剂流速。一个重要的发现是，电渗导致的通量增强强烈依赖于分子量（即，棉子糖的通量增强比大约是尿素的 4 倍，甘露醇和蔗糖产生中间值），而在每个电压下计算出的有效流速与渗透物的分子量无关。这与流速和施加电压之间的线性相关性一起，有助于确立该方法和模型的有效性。研究的第二阶段是将该模型扩展到人类表皮膜（HEM）。这些实验涉及在被动、250 mV 和 500 mV 条件下同时测量[14C]尿素和[3H]蔗糖跨 HEM 样品的通量。与核孔系统类似，在 HEM 中观察到的蔗糖的通量增强比大约是尿素的 3 倍。对 HEM 数据的详细分析表明，模型预测与实验结果之间存在半定量一致性。
