Interactions of Solutol HS 15 and Cremophor EL with plasma lipoproteins.
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.
Woodburn
K
K
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Sykes
E
E
Kessel
D
D
D000818:Animals; D001797:Blood Protein Electrophoresis; D001798:Blood Proteins / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D005990:Glycerol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000097:blood; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology*; D011166:Porphyrins / Q000097:blood; D011485:Protein Binding; D013229:Stearic Acids / Q000378:metabolism / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000378:metabolism / Q000494:pharmacology*
C089925:7,12-dioctyl-3,7,13,17-tetramethyl-8-porphinone-2,18-dipropionic acid; D001798:Blood Proteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017319:Photosensitizing Agents; D011166:Porphyrins; D013229:Stearic Acids; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C067028:Solutol HS 15; C000515:cremophor EL; D005990:Glycerol