The aggregation behavior of nystatin (NYS) in the presence of pluronic F127, triblock copolymer of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO), was measured and correlated with hemolytic activity. Antifungal activity was also studied using Saccharomyces cerevisiae as a model strain....
The aggregation behavior of nystatin (NYS) in the presence of pluronic F127, triblock copolymer of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO), was measured and correlated with hemolytic activity. Antifungal activity was also studied using Saccharomyces cerevisiae as a model strain. The critical aggregation concentrations (CAC) of the drug were 50.1, 108.0, 134.2, 154.3, and $217.9\;{\mu}M$ at 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% pluronic F127 solution, respectively. The levels of NYS required to start lysis of erythrocytes were about 80, 100, 125, 150, and $200\;{\mu}M$ at 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% pluronic F127 solution, respectively. It was $50\;{\mu}M$ in the absence of the polymer. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of NYS-pluronic F127 lyophilizate were same at $3\;{\mu}g/ml$, while MIC and MFC of pure NYS are $3\;{\mu}g/ml$ and $12\;{\mu}g/ml$, respectively. By modulating the aggregation behavior of NYS, pluronic F127 was able to reduce the toxicity of the drug without compromising the MIC and MFC.
The aggregation behavior of nystatin (NYS) in the presence of pluronic F127, triblock copolymer of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO), was measured and correlated with hemolytic activity. Antifungal activity was also studied using Saccharomyces cerevisiae as a model strain. The critical aggregation concentrations (CAC) of the drug were 50.1, 108.0, 134.2, 154.3, and $217.9\;{\mu}M$ at 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% pluronic F127 solution, respectively. The levels of NYS required to start lysis of erythrocytes were about 80, 100, 125, 150, and $200\;{\mu}M$ at 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% pluronic F127 solution, respectively. It was $50\;{\mu}M$ in the absence of the polymer. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of NYS-pluronic F127 lyophilizate were same at $3\;{\mu}g/ml$, while MIC and MFC of pure NYS are $3\;{\mu}g/ml$ and $12\;{\mu}g/ml$, respectively. By modulating the aggregation behavior of NYS, pluronic F127 was able to reduce the toxicity of the drug without compromising the MIC and MFC.
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가설 설정
The toxicity of polyene macrolide drug such as NYS and AmB has been repeatedly correlated to their self-aggregation state (3-4, 11). Given the similarity in structure to AmB and the effect of pluronic on the CAC, it is reasonable to hypothesize that interaction with the pluronic reduces the toxicity of the NYS through deaggregation.
제안 방법
To each tube, 50 µl of the inoculum which contained 5×103 cfu/ml of Saccharomyces cerevisiae in sterile distilled water was added, giving a total volume of 850 per tube, and incubated at 30℃ for 24h with vigorous agitation. A solvent control, pluronic F127 control, and medium control were performed simultaneously to check the growth inhibiting activities of DMSO, pluronic F127, and sterility of broth medium, respectively. The minimal inhibitory concentration (MIC) was defined as the minimum concentration of NYS that showed a fall inhibition of growth of Saccharomyces cerevisiae in tiie tube, determined by measuring the optical density at 600 nm.
대상 데이터
NYS was obtained from Sigma. Pluronic F127 was kindly donated by BASF Corporation. BactoTM YPD agar and BactoTM YPD broth were purchased from DIFCO Laboratories.
BactoTM YPD agar and BactoTM YPD broth were purchased from DIFCO Laboratories. Saccharomyces cereviciae (ATCC 4921) was purchased from ATCC. All other chemicals were analytical grade.
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