Hofland H E, van der Geest R, Bodde H E, Junginger H E, Bouwstra J A
Division of Pharmaceutical Technology, Leiden University, The Netherlands.
Pharm Res. 1994 May;11(5):659-64. doi: 10.1023/a:1018963910260.
The permeation of estradiol from vesicular formulations through human stratum corneum was studied in vitro. The vesicles were composed of nonionic n-alkyl polyoxyethylene ether surfactants (CnEOm). The thermodynamic activity of estradiol present in each formulation was kept constant by saturating all formulations with estradiol. The effects of both the particle size and the composition of the formulation on estradiol permeation across excised human stratum corneum were investigated. Stratum corneum that was pretreated with empty surfactant carriers allowed for significantly higher estradiol fluxes compared with untreated stratum corneum. However, estradiol fluxes obtained in these pretreatment experiments appeared to be significantly lower than those obtained by the direct application of the estradiol-saturated carrier formulation on top of the stratum corneum. Furthermore, in the case of pretreatment of the stratum corneum, an increase in carrier size resulted in a decrease in estradiol flux. For direct application the opposite was found. Two mechanisms are proposed to play an important role in vesicle-skin interactions, i.e., the penetration enhancing effect of surfactant molecules and the effect of the vesicular structures that are most likely caused by adsorption of the vesicles at the stratum corneum-suspension interface.
体外研究了雌二醇从囊泡制剂透过人体角质层的渗透情况。囊泡由非离子型正烷基聚氧乙烯醚表面活性剂（CnEOm）组成。通过用雌二醇使所有制剂饱和，使每个制剂中存在的雌二醇的热力学活性保持恒定。研究了制剂的粒径和组成对雌二醇透过离体人体角质层渗透的影响。与未处理的角质层相比，用空表面活性剂载体预处理的角质层允许显著更高的雌二醇通量。然而，在这些预处理实验中获得的雌二醇通量似乎明显低于通过将雌二醇饱和的载体制剂直接应用于角质层顶部所获得的通量。此外，在角质层预处理的情况下，载体尺寸的增加导致雌二醇通量的降低。对于直接应用，发现情况相反。提出两种机制在囊泡与皮肤的相互作用中起重要作用，即表面活性剂分子的渗透增强作用以及最有可能由囊泡在角质层 - 悬浮液界面的吸附引起的囊泡结构的作用。
