Optimization of transdermal delivery using magainin pore-forming peptide.
Optimization of transdermal delivery using magainin pore-forming peptide.
复制标题
DOI：
10.1016/j.jpcs.2007.10.138
复制
发表时间：
2008-05
期刊：
影响因子：
--
通讯作者：
Yeu‐Chun Kim;P. Ludovice;M. Prausnitz
中科院分区：
文献类型：
--
作者：
Yeu‐Chun Kim;P. Ludovice;M. Prausnitz
皮肤的外层角质层是含有多层脂质双层的薄组织，是药物通过皮肤递送的主要屏障。为了增加皮肤渗透性，我们先前的工作已经显示出使用成孔肽爪蟾抗菌肽（magainin）的经皮渗透的大幅增强，爪蟾抗菌肽与N-月桂酰肌氨酸（NLS）在50%乙醇-PBS中配制。机制分析表明，爪蟾抗菌肽和NLS可以通过破坏角质层脂质结构增加皮肤渗透性。在这项研究中，我们的目标是通过进一步优化爪蟾抗菌肽暴露的预处理时间和浓度来改善增加皮肤渗透性的条件。我们发现皮肤渗透性随着预处理时间的增加而增加。皮肤渗透性也随着爪蟾抗菌肽浓度的增加而增加，直到1 mM，但在爪蟾抗菌肽浓度为2 mM时降低。观察到皮肤对荧光素（332 Da）的渗透性增强高达35倍。相比之下，该制剂没有增强皮肤对较大分子的渗透性，例如钙黄绿素（623 Da）和葡聚糖（3000 Da）。
The skin's outer layer, stratum corneum, which is a thin tissue containing multilamellar lipid bilayers, is the main barrier to drug delivery through 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 1mM, but was reduced at a magainin concentration of 2mM. Enhancement of skin permeability to fluorescein (332Da) up to 35-fold was observed. In contrast, this formulation did not enhance skin permeability to larger molecules, such as calcein (623Da) and dextran (3000Da).