The alteration of plasma lipoproteins by cremophor EL

Abstract

Cremophor EL (CRM) is a non-ionic amphipathic emulsifier which has been used as a parenteral vehicle for many hydrophobic drugs. At concentrations above 0.4 mg ml −1, CRM alters lipoproteins so as to reduce their electrophoretic mobility; high density lipoprotein (HDL) is somewhat more sensitive than low density lipoprotein (LDL) in this regard. The same phenomenon was observed with Triton X-100 and Tween-80, two other non-ionic detergents. Ultracentrifugation experiments show that CRM alters the density of HDL resulting in a product with approximately the same specific gravity as LDL. Administration of mesoporphyrin solubilized with CRM to the mouse resulted in a rapid clearance of porphyrin bound to this new HDL species. Such a phenomenon may account for reports which indicate that CRM promotes the distribution of photosensitizing agents to neoplastic tissues.