Wearley L L, Tojo K, Chien Y W
Controlled Drug Delivery Research Center, Rutgers College of Pharmacy, Piscataway, NJ 08855-0789.
J Pharm Sci. 1990 Nov;79(11):992-8. doi: 10.1002/jps.2600791110.
The objective of this investigation was to quantitate the effect of binding on the iontophoretic transport of a series of amino acids. The diffusivity and concentration in the stratum corneum and viable skin were estimated from the passive permeation profiles through whole and stripped skin. Using these parameters and the Langmuir binding parameters from equilibrium binding studies, the passive permeation and desorption profiles were simulated using a bilayer skin permeation model. The parameters were adjusted until convergence with experimental data was achieved. Then the iontophoretic profiles were simulated, using the parameters from the simulated passive permeation studies, an estimate of convective flow from the flux of tritiated water, and measurement of the potential across the skin. The overall effect of binding on the iontophoretic profiles was found to dampen the effect of the iontophoresis treatment; the profiles appear flatter, and the transition to passive diffusion less distinct compared to profiles which do not include the binding parameters. It also appear that the degree of skin hydration has a substantial effect on the shape of the iontophoretic profile, such that approximately 50% of the enhancement in the iontophoretic profile of freshly excised skin continues after treatment.
本研究的目的是定量分析结合作用对一系列氨基酸离子导入转运的影响。通过完整皮肤和去角质皮肤的被动渗透曲线来估算角质层和活性皮肤中的扩散系数和浓度。利用这些参数以及平衡结合研究中的朗缪尔结合参数，采用双层皮肤渗透模型模拟被动渗透和解吸曲线。不断调整参数，直至与实验数据达到收敛。然后，利用模拟被动渗透研究中的参数、根据氚标记水通量估算的对流流量以及皮肤跨膜电位测量值，模拟离子导入曲线。结果发现，结合作用对离子导入曲线的总体影响是减弱离子导入治疗的效果；与未包含结合参数的曲线相比，这些曲线显得更平缓，向被动扩散的转变也不那么明显。此外，皮肤水合程度似乎对离子导入曲线的形状有重大影响，以至于新鲜切除皮肤的离子导入曲线增强效应在治疗后仍有大约50%得以持续。
