The alteration of plasma lipoproteins by cremophor EL.
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.
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
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D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D008652:Mesoporphyrins / Q000097:blood / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000097:blood / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology
D008074:Lipoproteins; D008652:Mesoporphyrins; D013501:Surface-Active Agents; C031468:mesoporphyrin IX; C000515:cremophor EL; D005990:Glycerol