| Summary: | 碩士 === 國立成功大學 === 化學工程學系碩博士班 === 95 === Paclitaxel is a promising anti-cancer agent but with poor water solubility (6 ppm (w/v)). The U.S. Food and Drug Administration has approved Taxol for use against breast cancer、ovarian cancer and non-small cell lung cancer. The current clinical formulation is 50:50 (v/v) mixture of cremophor EL and dehydrated ethanol which causes hypersensitivity reaction and precipitates upon dilution .So, we hope to solve the problems by the research.
The study focus on that mixed surfactant stabilized emulsion and larger amount of paclitaxel can be incorporated. First, it must find out suitable oils which can dissolve larger amount of drugs and posses biocompatibility. Furthermore, searching that the mixed surfactants can dissolve higher amount of screened oils. Thus, larger amounts of drugs can be encapsulated by the o/w emulsion. Moreover, the particle size of the emulsion ranges from 70nm to 200nm which meet the requirement for intravenous administration.
The research results reveal that tributyrin, ethyl caproate, ethyl caprylate have higher solubility for paclitaxel among the chosen oils including edible oils, triglycerides, fatty ester. The paclitaxel solubility in tributyrin, ethyl caproate and ethyl caprylate are around 28000 ppm (w/v), 12500 ppm (w/v) and 5000 ppm (w/v). We found out two more stable system in searching for mixed surfactant system. They are the combination of P 74/Tween 80 and P 74/ Cremopher EL. The two systems forms stable microemulsion by changing P 74/Tw 80 ratio from 0.66 to 1.5. The formulations contain 0.3%~0.5% tributyrin or 0.5%~0.8% ethyl caproate in the emulsion.Hence, up to 120~150 ppm of paclitaxel can be encapsulated and paclitaxel solubility was greatly enhanced.the paclitaxel delivery systems are promising and are worth further investigation.
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