Kim Yeu-Chun, Ludovice Peter J, Prausnitz Mark R
School of Chemical and Biomolecular Engineering Georgia Institute of Technology, Atlanta, GA 30332-0100.
J Phys Chem Solids. 2008 May;69(5-6):1560-1563. doi: 10.1016/j.jpcs.2007.10.138.
The skin's outer layer of stratum corneum, which is a thin tissue containing multilamellar lipid bilayers, is the main barrier to drug delivery to the skin. To increase skin permeability, our previous work has shown large enhancement of transdermal permeation using a pore-forming peptide, magainin, which was formulated with N-lauroyl sarcosine (NLS) in 50% ethanol-in-PBS. Mechanistic analysis suggested that magainin and NLS can increase skin permeability by disrupting stratum corneum lipid structure. In this study, our goal was to improve conditions that increase skin permeability by magainin by further optimizing the pretreatment time and concentration of magainin exposure. We found that skin permeability increased with increasing pretreatment time. Skin permeability also increased with increasing magainin concentration up to 1 mM, but was reduced at a magainin concentration of 2 mM. Enhancement of skin permeability to fluorescein (323 Da) up to 35-fold was observed. In contrast, this formulation did not enhance skin permeability to larger molecules, such as calcein (623 Da) and dextran (3,000 Da).
皮肤的最外层角质层是一种含有多层脂质双分子层的薄组织，是药物透皮递送的主要屏障。为了提高皮肤通透性，我们之前的研究表明，使用成孔肽蛙皮素可显著增强透皮渗透，蛙皮素与N-月桂酰肌氨酸（NLS）在50%乙醇-PBS中配制。机理分析表明，蛙皮素和NLS可通过破坏角质层脂质结构来增加皮肤通透性。在本研究中，我们的目标是通过进一步优化预处理时间和蛙皮素暴露浓度来改善蛙皮素增加皮肤通透性的条件。我们发现皮肤通透性随预处理时间的增加而增加。皮肤通透性也随蛙皮素浓度增加至1 mM而增加，但在蛙皮素浓度为2 mM时降低。观察到对荧光素（323 Da）的皮肤通透性增强高达35倍。相比之下，该制剂并未增强对较大分子如钙黄绿素（623 Da）和葡聚糖（3000 Da）的皮肤通透性。
