Lipid emulsions as a novel system to reduce the hemolytic activity of lytic agents: mechanism of the protective effect.
The hemolytic activity of sodium oleate, a high lytic agent, was investigated in different surfactant solutions and lipid emulsion formulations. A new explanation of the protective function of these systems is proposed. It was found that the hemolytic activity of the lytic agent was greatly decreased in solutions and/or dispersions with the surfactant Cremophor EL, Solutol H16 and phospholipids, which can usually build a micellar or liposomal structure. In the case of F68, where the micelle formation is still controversial, the hemolytic activity of the lytic agent was practically not affected and complete hemolysis was observed. In contrast to this, all emulsion formulations, independent of the emulsifier type, showed a stable erythrocyte behavior. Additionally, in the case of lipid emulsions only, a larger amount of the lytic agent could be added without any remarkable increase in the hemolytic activity. As an explanation for these effects it is proposed that the lytic agent is either incorporated into the lipophilic core or intercalates between the emulsifier molecules at the interface. This decreases the direct contact of the lytic agent with the erythrocyte membrane. As a result, the erythrocytes will effectively be protected from hemolytic damage, which can otherwise be induced by such substances.
Jumaa
M
M
Department of Pharmaceutics and Biopharmaceutics, Christian-Albrecht University, Gutenbergstr. 76, 24118, Kiel, Germany.
Müller
B W
BW
D000328:Adult; D004655:Emulsions; D004912:Erythrocytes / Q000187:drug effects; D005990:Glycerol / Q000031:analogs & derivatives; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D008823:Micelles; D019301:Oleic Acid / Q000737:chemistry* / Q000633:toxicity*; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols; D013229:Stearic Acids; D013501:Surface-Active Agents
D004655:Emulsions; D008081:Liposomes; D008823:Micelles; D010743:Phospholipids; D013229:Stearic Acids; D013501:Surface-Active Agents; D019301:Oleic Acid; C013173:osteum; D011092:Polyethylene Glycols; C000515:cremophor EL; D005990:Glycerol