Woodburn K, Sykes E, Kessel D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Int J Biochem Cell Biol. 1995 Jul;27(7):693-9. doi: 10.1016/1357-2725(95)00030-s.
Two emulsifying agents, Solutol HS15 and Cremophor EL, were compared with regard to their effects on human plasma lipoproteins in vitro and on mouse plasma lipoproteins in vitro and in vivo. Both agents promoted binding of a hydrophobic photosensitizing agent (C8KC) to a circulating plasma species of low bouyant density. Persistence of this material was greater with Cremophor than with Solutol. Experiments carried out with labeled Solutol indicated that the vehicle itself is a component of this new species. High concentrations of either vehicle ( > or = 0.06%) led to decreased electrophoretic mobility of human LDL and HDL in vitro. In the mouse, a different effect was observed, resulting in complex changes in electrophoretic mobility of plasma lipoproteins. The plasma half-life of C8KC in the circulation of the mouse was correlated with the persistence of an altered electrophoretic lipoprotein pattern. Since Solutol and C8KC showed similar half-lives, this result suggests that the plasma half-life of the sensitizer is correlated with the persistence of the vehicle. While Solutol and Cremophor were designed to be vehicles for drug formulation, they also influence persistence of some drugs in the circulation.
比较了两种乳化剂,聚乙二醇单硬脂酸酯(Solutol HS15)和聚氧乙烯蓖麻油(Cremophor EL),考察它们在体外对人血浆脂蛋白以及在体外和体内对小鼠血浆脂蛋白的影响。两种乳化剂均能促进一种疏水性光敏剂(C8KC)与循环中低密度血浆成分的结合。聚氧乙烯蓖麻油处理的这种物质的持久性高于聚乙二醇单硬脂酸酯处理的。用标记的聚乙二醇单硬脂酸酯进行的实验表明,载体本身是这种新成分的一个组成部分。两种载体的高浓度(≥0.06%)都会导致体外人低密度脂蛋白(LDL)和高密度脂蛋白(HDL)电泳迁移率降低。在小鼠中观察到了不同的效应,导致血浆脂蛋白电泳迁移率发生复杂变化。小鼠循环中C8KC的血浆半衰期与脂蛋白电泳图谱改变的持久性相关。由于聚乙二醇单硬脂酸酯和C8KC显示出相似的半衰期,该结果表明敏化剂的血浆半衰期与载体的持久性相关。虽然聚乙二醇单硬脂酸酯和聚氧乙烯蓖麻油被设计用作药物制剂的载体,但它们也会影响某些药物在循环中的持久性。