Spin Lapel Study on the Enhancement Mechanism of Transdermal Absorption Enhancers

我们研究了各种化合物对药物透皮吸收的促进作用的特征。在各种化合物中，n-烷基三甲基铵对相对亲水性药物表现出显着的增强作用。从苯甲酸4-烷基取代基的亚甲基从水相转移到皮肤的自由能对其渗透性数据的分析，这表明阳离子表面活性剂使皮肤相对更亲水。为了获得烷基化合物在皮肤中的定位信息，观察了离体豚鼠背部皮肤、角质层、去脂皮肤和角质层模型脂质体中烷基自旋标记物的电子自旋共振谱。根据分析，脂肪酸自旋标记物似乎存在于角质层的刚性脂质薄层中，脂肪酸酯自旋标记物存在于相对流体的环境中。另一方面，长链阳离子自旋标记物似乎存在于角质层的蛋白质区域中。后者的发现表明，阳离子表面活性剂与蛋白质的相互作用是其显着增强效果的原因。这些结果表明，不同的相互作用和不同的定位的烷基化合物取决于它们的电子电荷以及它们的烷基链的长度。我们进一步用自旋标记法研究了双链阳离子表面活性剂的分子组装体，揭示了其促进药物透皮吸收的机理。

We examined characteristics of enhancement effects of various compounds on transdermal drug absorption. Among various compounds n-alkyltrimethylammoniums showed marked enhancement effects on relatively hydrophilic drugs. From the analysis of the free energy of transfer of the methylene group of the 4-alkyl substituents of benzoic acid from the aqueous phase to skin on their permeability data, it was suggested that the cationic surfactants made the skin relatively more hydrophilic. To obtain the information on the localization of alkyl compounds in the skin, the electron spin resonance spectra of alkyl spin labels were observed in the excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes. According to the analysis fatty acid spin label seemed to be present in the stratum corneum rigid lipid lamella, fatty acid ester spin label in the relatively fluid environment. On the other hand, long-chain cationic spin label seemed to be present in the protein region of the stratum corneum. The latter finding suggested that the interaction of the cationic surfactants with the proteins was the reason for their significant enhancement effects. These findings indicated that the different interaction and different localization of the alkyl compounds depended on their electronic charge as well as their alkyl chain lengths. We furthermore studied the molecular assemblies of double-chained cationic surfactants by spin label study and revealed their enhancement mechanism on transdermal drug absorption.