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. 1989 Mar;33(3):345–349. doi: 10.1128/aac.33.3.345

Study of the effects of liposomal amphotericin B on Candida albicans, Cryptococcus neoformans, and erythrocytes by using small unilamellar vesicles prepared from saturated phospholipids.

S Jullien 1, A Contrepois 1, J E Sligh 1, Y Domart 1, P Yeni 1, J Brajtburg 1, G Medoff 1, J Bolard 1
PMCID: PMC171491  PMID: 2658784

Abstract

We compared the anticellular effects of liposomal amphotericin B (AmB) formed from AmB and small unilamellar vesicles. The small unilamellar vesicles with or without cholesterol were prepared from three L-alpha-phosphatidylcholines with saturated acyl chains of different lengths: distearoyl (C18), dipalmitoyl (C16), and dimyristoyl (C14). We found that the anticellular potency of liposomal AmB, compared with that of free AmB, decreased with decreasing length of the acyl chain of the phospholipid and increased with the addition of cholesterol. In a parallel study (S. Jullien, A. Vertut-Croquin, J. Brajtburg, and J. Bolard, Anal. Biochem. 172:197-202, 1988), we found that binding of AmB to vesicles decreased with increasing length of the acyl chain of the phospholipid and decreased with the addition of cholesterol. We conclude that the anticellular effects of liposomal AmB preparations are due to the levels of AmB remaining free (unbound to the lipids) in these preparations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bolard J., Cheron M. Association of the polyene antibiotic amphotericin B with phospholipid vesicles: perturbation by temperature changes. Can J Biochem. 1982 Aug;60(8):782–789. doi: 10.1139/o82-097. [DOI] [PubMed] [Google Scholar]
  2. Chen W. C., Bittman R. Kinetics of association of amphotericin B with vesicles. Biochemistry. 1977 Sep 20;16(19):4145–4149. doi: 10.1021/bi00638a002. [DOI] [PubMed] [Google Scholar]
  3. Janoff A. S., Boni L. T., Popescu M. C., Minchey S. R., Cullis P. R., Madden T. D., Taraschi T., Gruner S. M., Shyamsunder E., Tate M. W. Unusual lipid structures selectively reduce the toxicity of amphotericin B. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6122–6126. doi: 10.1073/pnas.85.16.6122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Juliano R. L., Grant C. W., Barber K. R., Kalp M. A. Mechanism of the selective toxicity of amphotericin B incorporated into liposomes. Mol Pharmacol. 1987 Jan;31(1):1–11. [PubMed] [Google Scholar]
  5. Juliano R. L., Lopez-Berestein G., Hopfer R., Mehta R., Mehta K., Mills K. Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections. Ann N Y Acad Sci. 1985;446:390–402. doi: 10.1111/j.1749-6632.1985.tb18416.x. [DOI] [PubMed] [Google Scholar]
  6. Jullien S., Vertut-Croquin A., Brajtburg J., Bolard J. Circular dichroism for the determination of amphotericin B binding to liposomes. Anal Biochem. 1988 Jul;172(1):197–202. doi: 10.1016/0003-2697(88)90432-0. [DOI] [PubMed] [Google Scholar]
  7. Mehta R., Lopez-Berestein G., Hopfer R., Mills K., Juliano R. L. Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim Biophys Acta. 1984 Mar 14;770(2):230–234. doi: 10.1016/0005-2736(84)90135-4. [DOI] [PubMed] [Google Scholar]
  8. Newman G. C., Huang C. Structural studies on phophatidylcholine-cholesterol mixed vesicles. Biochemistry. 1975 Jul 29;14(15):3363–3370. doi: 10.1021/bi00686a012. [DOI] [PubMed] [Google Scholar]
  9. Sokol-Anderson M. L., Brajtburg J., Medoff G. Amphotericin B-induced oxidative damage and killing of Candida albicans. J Infect Dis. 1986 Jul;154(1):76–83. doi: 10.1093/infdis/154.1.76. [DOI] [PubMed] [Google Scholar]
  10. Stewart J. C. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem. 1980 May 1;104(1):10–14. doi: 10.1016/0003-2697(80)90269-9. [DOI] [PubMed] [Google Scholar]
  11. Szoka F. C., Jr, Milholland D., Barza M. Effect of lipid composition and liposome size on toxicity and in vitro fungicidal activity of liposome-intercalated amphotericin B. Antimicrob Agents Chemother. 1987 Mar;31(3):421–429. doi: 10.1128/aac.31.3.421. [DOI] [PMC free article] [PubMed] [Google Scholar]

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