Lambert W J, Higuchi W I, Knutson K, Krill S L
Department of Pharmaceutics, University of Utah, Salt Lake City 84112.
Pharm Res. 1989 Sep;6(9):798-803. doi: 10.1023/a:1015931715829.
In vitro permeability experiments have been combined with differential scanning calorimetry (DSC) studies in an attempt to address the dose-dependent influence of Azone on the permeability coefficients of solutes for hairless mouse stratum corneum. A spray technique was developed to deliver uniformly and quantitatively small amounts of Azone to the stratum corneum. Permeability data obtained for several model solutes of varying lipophilicity suggest lipid fluidization and polar route enhancement as the mechanisms of action for Azone. Alkanols and steroids, both of which are enhanced primarily by lipid fluidization, had different degrees of relative enhancement. This provides evidence that the stratum corneum barrier is heterogeneous, rather than a homogeneous slab barrier. Two effects of Azone on the stratum corneum were detected by DSC. A decrease in the area and a shift to lower temperatures were noted for the lipid endotherms with increasing doses of Azone. A lipid fluidizing effect would qualitatively account for the increases in the permeability coefficients noted for more lipophilic solutes. The stratum corneum keratin endotherm also appears to be altered in the presence of Azone. It is possible that alteration of the keratin structure could lead to the development of polar routes in the stratum corneum.
体外渗透实验已与差示扫描量热法（DSC）研究相结合，旨在探讨氮酮对无毛小鼠角质层中溶质渗透系数的剂量依赖性影响。开发了一种喷雾技术，以便将少量氮酮均匀且定量地递送至角质层。针对几种不同亲脂性的模型溶质获得的渗透数据表明，脂质流化和极性途径增强是氮酮的作用机制。主要通过脂质流化增强的链烷醇和类固醇具有不同程度的相对增强。这提供了证据，表明角质层屏障是异质性的，而非均匀的平板屏障。通过DSC检测到氮酮对角质层有两种影响。随着氮酮剂量增加，脂质吸热峰的面积减小且向更低温度偏移。脂质流化效应从定性上解释了亲脂性更强的溶质的渗透系数增加的现象。在氮酮存在的情况下，角质层角蛋白吸热峰似乎也发生了改变。角质层结构的改变可能导致角质层中极性途径的形成。
