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Micelle, Liposome, Polyethylene Glycol을 이용한 Amphotericin B의 세포막 독성저하
박인철,이판종,양지원,김종득,최태부 한국산업미생물학회 1994 한국미생물·생명공학회지 Vol.22 No.3
Amp. B의 세포막 독성을 낮추기 위하여 mixed micelle, PEG, liposome의 세 system을 이용하였다. Cholesterol-sulfate와 Amp. B의 mixed micelle은 Amp. B의 적혈구 세포막에 대한 독성을 낮추는데 매우 효과적이었다. 0.01%의 cholestrol-sulfate는 5×10exp(-6)의 Amp. B의 독성을 90%까지 낮추었으며 높은 농도의 Amp. B에서는 비례적으로 높은 농도의 cholesterol-sulfate가 요구되었다. 이에 반해 PEG는 Amp. B의 농도에는 상관 없이 50%의 독성을 낮추는데 2%의 PEG가 필요하였다. 이는 PEG가 Amp. B와 친화력이 존재하여 효과가 나타났다기 보다는 PEG가 Amp. B의 확산을 방해하여 나타난 결과로 판단된다. Liposome system에서는 Amp. B의 항생효과를 그대로 유지하면서도 적혈구에 대한 세포막 독성을 현저히 감소시켰다. 이는 liposome 이중막이 fungi(Candida albicans)의 세포막에 존재하는 ergosterol과 적혈구의 세포막에 존재하는 cholesterol 사이에서 약물의 재분배를유도하였기 때문에 나타난 현상으로 판단된다. Micelle, liposome and polyethylene glycol(PEG) were employed to reduce the cell membrane 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 5×10exp(-6)M Amp. B by 90%. The required concentration 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.
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Reduction of Cell Membrane Toxicity of Amphotericin B Using Micelle,Liposome and Polyethyene Glycol
박인철,이판종,양지원,김종득,최태부,Park, In-Chul,Lee, Pan-Jong,Yang, Ji-Won,Kim, Jong-Deuk,Choe, Tae-Boo 한국미생물 · 생명공학회 1994 한국미생물·생명공학회지 Vol.22 No.3
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.
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