Use of Liposomes on Modification of Stratum Corneum Lipids and Enhancement of Transdermal Drug Permeation

为了将脂质和脂质类似物有效地输送到皮肤，我们研究了含有双链阳离子表面活性剂的阳离子脂质体的稳定性，脂质体与红细胞膜的相互作用以及脂质体与皮肤的相互作用。二甲基二棕榈酰铵形成稳定的脂质体中存在的磷脂酰胆碱与不饱和的酰基链，而1，2-二油酰基-3-三甲基铵丙烷形成稳定的脂质体，即使在存在的磷脂酰胆碱与饱和的酰基链。这些阳离子脂质体诱导红细胞的聚集和融合。通过使用脂质体与生物膜的这种相互作用，我们试图将神经酰胺递送到脂质缺乏的皮肤。我们证实，神经酰胺和二甲基-二棕榈基铵形成稳定的双层囊泡胆固醇的存在下，在摩尔比为1：1：1。将阳离子脂质体添加到80%乙醇处理的脱脂豚鼠背部皮肤中，略微恢复了角质层脂质层的刚度，并有恢复其屏障功能的趋势。此外，我们发现使用阳离子脂质体增强了视黄酸的掺入。通过这些发现，我们阐明了阳离子脂质体有效递送脂质和脂质类似物至皮肤的有用性。

With the aim of efficient delivery of lipids and lipid analogs to skin, we studied the stability of cationic liposomes containing double-chained cationic surfactants, the interaction of the liposomes with erythrocyte membrane as well as that with skin. Dimethyldipalmitylammonium formed stable liposomes in the presence of phosphatidylcholines with unsaturated acy1 chains, whereas 1,2-dioleoyl-3-trimethylammonium propane formed the stable liposomes even in the presence of phosphatidylcholines with saturated acy1 chains. These cationic liposomes induced aggregation and fusion of the erythrocytes. By using such interaction of the liposomes with biological membranes we tried to deliver ceramide to lipid deficient skin. We confirmed that ceramide and dimethyl-dipalmitylammonium formed stable bilayer vesicles in the presence of cholesterol at a molar ratio of 1:1:1. The addition of the cationic liposomes to 80% ethanol-treated delipidized guinea pig dorsal skin slightly recovered the rigidity of the stratum corneum lipid lamella and had a tendency to recover its barrier function. We furthermore found the enhanced incorporation of retinoic acid using cationic liposomes. Through these findings we clarified the usefulness of the cationic liposomes to efficient delivery of lipids and lipid analogs to skin.