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2002 | 49 | 1 | 67-75
Article title

Comparative in vitro studies on liposomal formulations of amphotericin B and its derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME).

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EN
Abstracts
EN
N-Methyl-N-D-fructosyl amphotericin B methyl ester (MFAME) is a semisynthetic derivative of the antifungal antibiotic amphotericin B (AMB). In contrast to the parent antibiotic, the derivative is characterised by low toxicity to mammalian cells and good solubility in water of its salts. Comparative studies on biological properties of free MFAME, AMB and their liposomal formulations were performed. To obtain liposomal forms, the antibiotics were incorporated into small unilamellar vesicles composed of dimyristoyl phosphatidylcholine (DMPC) and DMPC:cholesterol or ergosterol, 8:2 molar ratio. The effectivity of the liposomal and free forms of AMB and MFAME were compared by determination of fungistatic and fungicidal activity against Candida albicans ATCC 10261, potassium release from erythrocytes, and haemolysis. The results obtained indicate that in contrast to AMB, incorporation of MFAME into liposomes did not further improve its selective toxicity. Studies on the antagonistic effect of ergosterol and cholesterol on the antifungal activity of the antibiotics indicated that sterol interference was definitely less pronounced in the case of MFAME than in the case of AMB.
Publisher

Year
Volume
49
Issue
1
Pages
67-75
Physical description
Dates
published
2002
received
2001-09-10
revised
2002-01-20
accepted
2002-02-14
Contributors
  • Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, 80-952 Gdańsk, Poland
  • Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, 80-952 Gdańsk, Poland
  • Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, 80-952 Gdańsk, Poland
  • Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, 80-952 Gdańsk, Poland
References
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  • 2. Brajtburg, J. & Bolard, J. (1996) Carrier effects on biological activity of amphotericin B. Clin. Microbiol. Rev. 9, 512-531.
  • 3. Grzybowska, J., Sowiński, P., Gumieniak, J., Zieniawa, T. & Borowski, E. (1997) N-methyl-N-D-fructopyranosyloamphotericin B methyl ester, new amphotericin B derivative of low toxicity. J. Antibiotics 50, 709-711.
  • 4. Szlinder-Richert, J, Cybulska, B., Grzybowska, J., Borowski, E. & Prasad, R. (2000) Comparative studies on cell’s stimulatory, permeabilizing and toxic effects induced in sensitive and multidrug resistant fungal strains by amphotericin B (AMB) and N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME). Acta Biochim. Polon. 47, 133-140.
  • 5. Hiemenez, J.W. & Walsh, T.J. (1996) Lipid formulation of amphotericin B: Recent progress and future directions. Clin. Infec. Dis. 22, 133-144.
  • 6. Lampen, J.O., Arnow, P.M. & Safferman, R.S. (1960) Mechanism of protection by sterols against polyene antibiotics. J. Bacteriol. 80, 200-206.
  • 7. Newman, G.C. & Huang, C. (1975) Structural studies on phosphatidyl-cholesterol mixed vesicles. Biochemistry 14, 3363-3367.
  • 8. Jullien, S., Contrepois, A., Sligh, J.E., Domart, Y., Yeni, P., Brajtburg, J., Medoff, G. & Bolard, J. (1989) Study of the effects of liposomal amphotericin B on Candida albicans, Cryptococcus neoformans and erythrocytes by using small unilamellar vesicles prepared from saturated phospholipids. Antimicrob. Agents Chemother. 33, 345-349.
  • 9. Legrand, P., Romero, E.A., Cohen, B.E. & Bolard, J. (1992) Effects of aggregation and solvent on the toxicity of amphotericin B to human erythrocytes. Antimicrob. Agents Chemother. 36, 2518-2522.
  • 10. Bolard, J., Legrand, P., Heitz, F. & Cybulska, B. (1991) One-sided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium. Biochemistry 30, 5707-5715.
  • 11. Gruda, I., & Dussault, N. (1988) Effect of aggregation state of amphotericin B on its interaction with ergosterol. Biochem. Cell Biol. 66, 177-183.
  • 12. Barwicz, J. & Tancrede, P. (1997) The effect of aggregation state of amphotericin B on its interaction with cholesterol-or ergosterol-containing phosphatidylcholine monolayers. Chem. Phys. Lipids 85, 145-155.
  • 13. Szlinder-Richert, J., Mazerski, J., Cybulska, B., Grzybowska, J. & Borowski, E. (2001) MFAME, N -methyl-N-D-fructosyl amphotericin B methyl ester, a new amphotericin B derivative of low toxicity: Relationship between self-association and effects on red blood cells. Biochim. Biophys. Acta 1528, 15-24.
  • 14. Cybulska, B., Gadomska, I., Mazerski, J., Grzybowska, J., Borowski, E., Cheron, M. & Bolard, J. (2000) N-Methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME), a novel antifungal agent of low toxicity: Monomer/micelle control over selective toxicity. Acta Biochim. Polon. 47, 121-131.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv49i1p67kz
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