Tokudome Yoshihiro, Saito Yuko, Sato Fumihiko, Kikuchi Maki, Hinokitani Toshihiro, Goto Kenichi
Cutaneous Drug Research Laboratories, POLA Chemical Industries, INC., 244-0812 Yokohama, Japan.
Colloids Surf B Biointerfaces. 2009 Oct 1;73(1):92-6. doi: 10.1016/j.colsurfb.2009.05.002. Epub 2009 May 13.
Liposomes are useful vesicles that deliver drugs effectively to various organs. For transdermal applications, liposomes with high membrane fluidity, high fusion activity, and comprising stratum corneum lipid have been used for drug delivery. With the aim to increase drug distribution to the skin, we developed new liposomes with three characteristics: high membrane fluidity, high fusion activity to the stratum corneum lipid liposomes (SCLL), and lipid compositions based on stratum corneum lipids. New liposomes were prepared based on SCLL. First, lipid compositions of SCLL were optimized. Second, the alkyl chain length of ceramides and fatty acids, and the saturation degree of fatty acids were altered. As a result, liposomes with the highest membrane fluidity and fusion activity to SCLL were composed of C-8 ceramide/cholesterol/linolenic acid/cholesterol sulfate = 45/5/5/45 (w/w%), and named C8L. C8L had 1.54-times greater membrane fluidity and 6.57-times greater fusion activity to SCLL than SCLL. Transmission electron microscopy revealed that C8L had a spherical structure. The surface charge and the particle size were approximately -47.7 mV and 184 nm, respectively. Thus, in the future, C8L will be used to facilitate drug delivery to the skin.
脂质体是一种有用的囊泡，可将药物有效地递送至各个器官。对于透皮应用，具有高膜流动性、高融合活性且包含角质层脂质的脂质体已被用于药物递送。为了增加药物在皮肤中的分布，我们开发了具有三个特性的新型脂质体：高膜流动性、对角质层脂质体（SCLL）的高融合活性以及基于角质层脂质的脂质组成。基于SCLL制备了新型脂质体。首先，优化了SCLL的脂质组成。其次，改变了神经酰胺和脂肪酸的烷基链长度以及脂肪酸的饱和度。结果，具有最高膜流动性和对SCLL融合活性的脂质体由C-8神经酰胺/胆固醇/亚麻酸/硫酸胆固醇 = 45/5/5/45（w/w%）组成，并命名为C8L。C8L的膜流动性比SCLL高1.54倍，对SCLL的融合活性比SCLL高6.57倍。透射电子显微镜显示C8L具有球形结构。表面电荷和粒径分别约为-47.7 mV和184 nm。因此，未来C8L将用于促进药物向皮肤的递送。
