Reduction of Cell Membrane Toxicity of Amphotericin B Using Micelle,Liposome and Polyethyene Glycol

Micelle, Liposome, Polythylene Glycol을 이용한 Amphotericin B의 세포막 독성저하

  • 박인철 (건국대학교 공과대학 미생물공학과) ;
  • 이판종 (건국대학교 공과대학 미생물공학과) ;
  • 양지원 (한국과학기술원 화학공학과) ;
  • 김종득 (한국과학기술원 화학공학과) ;
  • 최태부 (건국대학교 공과대학 미생물공학과)
  • Published : 1994.06.01

Abstract

Micelle, liposome and polyethylene glycol(PEG) were employed to reduce the cell mem- brane toxicity of Amphotericin B(Amp. B). Cholesterol-sulfate which can form a mixed micelle with Amp. B molecules was found very effective for the reduction of Amp. B toxicity. 0.01% of cholesterol-sulfate could reduce the toxicity of 5X 10$^{-6}$ M Amp. B by 90%. The required concent- ration of cholesterol-sulfate for the toxicity reduction was proportionally increased with increasing Amp. B concentration. PEG was also effective on the reduction of Amp. B toxicity. 2% PEG was required for the reduction of toxicity by 50%, regardless of Amp. B concentration. The liposome system showed an effective reduction of Amp. B toxicity on RBC, maintaining the antibiotic effect on Candida albicans as free drugs. This seems to be due to the fact that liposome bilayer plays a role of buffer system between ergosterol of fungi cell membrane and cholesterol of red blood cell membrane, which leads the redistribution of Amp. B between them, as the result, the reduction of drug toxicity on cell membrane.

Keywords

References

  1. Bact. Rev. v.37 Chemistry and biology of the polyene macrolide antibiotics Hamillton,J.H.T.;Miller
  2. Ann. Rev. Pharmacol. v.119 Antibiotic interaction with model membrane Kinsky,S.C.
  3. Antibiotics,(2nd ed.) Holtz,R.W.
  4. Ann. N.Y. Acad. Sci. v.202 Experience with amphotericin B. Seaberg,J.H.;H.E.Dascomb
  5. Am. J. Dis. Child. v.731 Toxicity of Amphotericin B in Childern with Cancer Wilson,R.;S.Feldman
  6. The J. Infectious Disease v.152 Distribution and acitivity of amphotericin B in human Keryn, J.C.;M.B.Edward;W.M.G.Jonathan;A.Donard
  7. Recent progress in antifungal chemotherapy Hideo,Y.;S.K.George;T.Hisashi
  8. Antimicrobial Agents and Chemotherapy v.26 Efficacy of liposome-intercalated amphotericin B in the treatment of systemic candidiasis in mice Claude,T.;B.Michael;F.Cynthia;S.Francis
  9. Liposome technique v.1 Gregory,G.
  10. Biochimica et Biophysica Acta v.1021 The affinity of amphotericin B to lipid bilayer Soitic J.