Woodburn K, Kessel D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Int J Biochem Cell Biol. 1995 May;27(5):499-506. doi: 10.1016/1357-2725(95)00015-h.
The binding of photosensitizing agents to low-density lipoprotein is considered an important factor in tumor localization. We examined the affinity of a group of photosensitizers, varying in charge and hydrophobicity, for LDL, under conditions designed to determine whether the high salt concentration involved in conventional KBr gradients affected the results. Density-gradients containing KBr vs D2O were evaluated; the latter can delineate VLDL and LDL from other plasma components, while the KBr gradient readily resolved VLDL, LDL, HDL and albumin. Distribution of the photosensitizers to plasma fractions was assessed, along with the effect of Cremophor EL, an emulsifier used for formulation of water-insoluble drugs. Both the D2O and KBr gradients provided similar results with regard to the affinity of anionic, neutral or cationic photosensitizers for LDL. The use of Cremophor EL for drug formulation was associated with an altered electrophoretic lipoprotein profile. In some cases, affinity of CRM-solubilized sensitizers for plasma components varied with the density-gradient employed. The high salt concentration used in density-gradient fractionation had little effect on the affinity of photosensitizing agents to low-density lipoprotein but may introduce artifacts when emulsifiers are used in drug formulation.
光敏剂与低密度脂蛋白的结合被认为是肿瘤定位的一个重要因素。我们在旨在确定传统溴化钾梯度中涉及的高盐浓度是否会影响结果的条件下，研究了一组电荷和疏水性各异的光敏剂对低密度脂蛋白的亲和力。评估了含溴化钾与重水的密度梯度；后者可将极低密度脂蛋白和低密度脂蛋白与其他血浆成分区分开来，而溴化钾梯度能轻松分离极低密度脂蛋白、低密度脂蛋白、高密度脂蛋白和白蛋白。评估了光敏剂在血浆组分中的分布，以及聚氧乙烯蓖麻油（一种用于配制水不溶性药物的乳化剂）的影响。就阴离子、中性或阳离子光敏剂对低密度脂蛋白的亲和力而言，重水和溴化钾梯度给出了相似的结果。使用聚氧乙烯蓖麻油进行药物配制与脂蛋白电泳图谱改变有关。在某些情况下，聚氧乙烯蓖麻油增溶的光敏剂对血浆成分的亲和力随所用密度梯度而变化。密度梯度分级分离中使用的高盐浓度对光敏剂与低密度脂蛋白的亲和力影响很小，但在药物配制中使用乳化剂时可能会引入假象。
