Alteration of the permeability of the human erythrocyte membrane to cations by liposome-incorporated amphotericin B.
Some effects of liposome-incorporated amphotericin B on the permeability of the human erythrocyte membrane to potassium and sodium ions is reported. The influence of cholesterol and amphotericin B in causing a shift towards smaller and larger liposomes, respectively, is also described. Phosphatidylcholine liposomes containing amphotericin B in a molar ratio of 7.4 +/- 0.1 (mean +/- SD) antibiotic to 1000 phospholipid reduced the initial rates of K+ and Na+ transport across the erythrocyte membrane to 40 +/- 2.6% and 0%, respectively, of their rates in the presence of comparable concentrations of free amphotericin B. Amphotericin B incorporated into liposomes (8.2 +/- 0.15 mumol antibiotic per 1000 mumol total lipid) composed of cholesterol and phosphatidylcholine (in a molar ratio of 3:7) reduced the initial rate of K+ transport to 19 +/- 0.8% of its value measured in the presence of a comparable concentration of free antibiotic. These results suggest that liposomes containing specified amounts of amphotericin B, especially liposomes also containing cholesterol in addition to phosphatidylcholine, could be used as a method of controlling K+ transport across the erythrocyte and possibly other types of cellular membranes, thereby limiting antibiotic toxicity to some mammalian tissues.
Abu-Salah
K M
KM
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D010316:Particle Size; D010713:Phosphatidylcholines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D008081:Liposomes; D010713:Phosphatidylcholines; D000666:Amphotericin B; D002784:Cholesterol; D012964:Sodium; D011188:Potassium