Woodburn K, Chang C K, Lee S, Henderson B, Kessel D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
Photochem Photobiol. 1994 Aug;60(2):154-9. doi: 10.1111/j.1751-1097.1994.tb05083.x.
C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a lipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.
C8KC是一种新型的酮氯卟啉光敏剂，因其水溶性差，必须与乳化剂一起配制。在本报告中，我们比较了聚氧乙烯蓖麻油（CRM）和吐温80作为C8KC载体的性质。与吐温80不同，CRM改变了人和小鼠血浆脂蛋白的物理性质，导致各脂蛋白的电泳迁移率降低，并形成脂蛋白降解产物：低浮力密度的磷脂部分。在人血浆中，有足够的低密度脂蛋白（LDL）可供区分，CRM导致酮氯卟啉从白蛋白向LDL和降解的脂蛋白部分转移。在携带RIF肿瘤的小鼠中，使用CRM进行药物配制与C8KC在血浆和组织中的持续时间延长以及光动力疗法（PDT）疗效增强有关。这些结果表明敏化剂和载体作为PDT疗效决定因素的重要性。
