Influence of molecular dipoles on human skin permeability: Use of 6-ketocholestanol to enhance the transdermal delivery of bacitracin
Influence of molecular dipoles on human skin permeability: Use of 6-ketocholestanol to enhance the transdermal delivery of bacitracin
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DOI：
10.1002/jps.10344
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发表时间：
2003-05-01
影响因子：
3.8
通讯作者：
Valenta, C
中科院分区：
文献类型：
--
作者：
Cladera, J;O'Shea, P;Valenta, C
在目前的工作中，我们报告了用结构具有大分子偶极矩的化合物处理人体表皮来改变皮肤静电特性的可能性。数据显示，这种修饰可以用来增强皮肤给药。这些化合物在生物膜中的包含会影响所谓的膜偶极子电位，这是一种源于存在于脂质分子上的分子偶极子的电位。已知这种电位大小的改变会影响疏水离子和多肽与模型膜的相互作用。使用荧光素标记的杆菌肽和共聚焦显微镜，我们发现，当皮肤用含有30 mol % 6-酮胆甾醇的脂体预处理时，抗生素肽杆菌肽对表皮的渗透增强，这种化合物已知可以增加膜偶极子电位的大小。利用荧光指示剂荧光素对磷脂酰乙醇胺和1-（3-磺基丙基）-4-[β -[2-（二-正辛胺）-6-萘基]乙烯基]吡啶甜菜碱的研究表明，6-酮胆甾醇的存在也增强了杆菌肽与模型膜的相互作用，并对穿透增强的机制提供了一些指示。(C) 2003 Wiley-Liss, Inc.和美国制药协会。
In the present work, we report the possibility of modifying the electrostatic properties of the skin by treating human epidermis with compounds whose structures possess a large molecular dipole moment. Data are presented showing that such a modification can be used to enhance dermal drug delivery. Inclusion of such compounds in biological membranes affects the so-called membrane dipole potential, an electrical potential originating from molecular dipoles present on the lipid molecules. Modifications in the magnitude of this potential are known to affect the interaction of hydrophobic ions and peptides with model membranes. Using fluorescein-labeled bacitracin and confocal microscopy, we show that the penetration of the antibiotic peptide bacitracin into the epidermis is enhanced when the skin has been pretreated with liposomes loaded with 30 mol % 6-ketocholestanol, a compound known to increase the magnitude of the membrane dipole potential. Studies using the fluorescent indicators fluoreseeinphosphatidylethanolamine and 1-(3-sulfonatopropyl)-4-[beta [2-(di-n-octylamino)-6-naphthyl] vinyl] pyridinium betaine show that the interaction of bacitracin with model membranes is also enhanced by the presence of 6-ketocholestanol in the bilayer and offers some indication to the mechanism of penetration enhancement. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association.