López-Castellano A, Cortell-Ivars C, López-Carballo G, Herráez-Domínguez M
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia. Universidad de Valencia, Avd. Vicente Andrés Estellés s/n. 46100, Burjassot, Spain.
Int J Pharm. 2000 Aug 10;203(1-2):245-53. doi: 10.1016/s0378-5173(00)00463-4.
Recently we have proved that Span 20 has the same enhancer effect as Azone on in vitro percutaneous penetration of lipophilic compounds (logP(oct) from 1.34 to 2.33). The purpose of this work is to study the interactions of Span 20 with stratum corneum lipids monolayers and to compare them with Azone. The surface pressure-area characteristics of Span 20 in mixed monolayers with different model lipids (ceramides, cholesterol, free fatty acids and two mixtures of ceramides+cholesterol, and ceramides+cholesterol+free fatty acids) in similar proportions to that which exists in human stratum corneum lipids were recorded as compression isotherms at 25 degrees C. Azone was also investigated on monomolecular films of some of these lipids. The results indicate that the effect exerted upon lipid packing by the Span 20 correspond, as in the case of Azone, to increased fluidity within monolayers. To quantify and compare the effect of Span 20 and Azone, the compressibility of enhancer-lipid model mixed monolayers was calculated, and expressed as a function of mole fraction of enhancer present on the films. Statistical comparison of the results obtained from both enhancers shows that they are equally potent in their interaction with the lipid models assayed. These models, if restricted, seem to be good for predict the activity and potency of percutaneous enhancers on the fluididity of the lipidic structure of the stratum corneum.
最近我们已证明，Span 20对亲脂性化合物（logP（辛醇）为1.34至2.33）的体外经皮渗透具有与氮酮相同的增强作用。这项工作的目的是研究Span 20与角质层脂质单层的相互作用，并将其与氮酮进行比较。在25℃下，以压缩等温线记录Span 20与不同模型脂质（神经酰胺、胆固醇、游离脂肪酸以及神经酰胺+胆固醇和神经酰胺+胆固醇+游离脂肪酸的两种混合物）按与人角质层脂质中存在的比例相似的比例形成的混合单层的表面压力-面积特性。还研究了氮酮在其中一些脂质的单分子膜上的情况。结果表明，与氮酮的情况一样，Span 20对脂质堆积产生的作用相当于单层内流动性的增加。为了量化和比较Span 20和氮酮的作用，计算了增强剂-脂质模型混合单层的压缩性，并表示为膜上存在的增强剂摩尔分数的函数。对两种增强剂所得结果的统计比较表明，它们在与所测定的脂质模型的相互作用中效力相当。这些模型，如果加以限制，似乎有助于预测经皮增强剂对角质层脂质结构流动性的活性和效力。
