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Development of a micelle-fractional precipitation hybrid process for the pre-purification of paclitaxel from plant cell cultures
Institution:1. Department of Chemical Engineering, Kongju National University, 182 Shinkwan-Dong, Kongju 314-701, South Korea;2. Department of Chemical Engineering, Hanyang University, Haengdang-dong, Seongdong-gu, Seoul 133-791, South Korea;1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY;2. Departments of Medical Physics and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY;3. Genelux Corporation, San Diego Science Center, San Diego, CA;4. Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California San Diego, San Diego, CA;5. Department of Biochemistry, Rudolf Virchow Center for Experimental Biomedicine, and Institute for Molecular Infection Biology, University of Würzburg, Am Hubland, Würzburg, Germany;1. Department of Chemical Engineering, Hanyang University, Seoul, 133-791, South Korea;2. Department of Fuel Cells and Hydrogen Technology, Hanyang University, Seoul, 133-791, South Korea;3. Department of Chemical Engineering, Kongju National University, Cheonan, Chungnam, 331-717, South Korea
Abstract:A micelle-fractional precipitation hybrid process was developed for the effective pre-purification of the anticancer agent paclitaxel extracted from plant cell cultures. First, it was found that the efficiency of such a developed process could be remarkably enhanced by removing waxy substances originating from plant cells using the adsorbent sylopute. Paclitaxel yield was improved and the fractional precipitation time was shortened by increasing the surface area per working volume (S/V) of the reacting solution through the addition of a cation exchange resin (Amberlite IR120 or Amberlite 200), an anion exchange resin (Amberlite IRA400 or Amberlite IRA96), or glass beads. Most of the paclitaxel (>98%) could be obtained after about 12 h of fractional precipitation using Amberlite 200. Purity increased with increasing fractional precipitation time up to 9 h to about 85%, after which it showed little change. On the other hand, no paclitaxel precipitate was formed using either of the nonionic exchange resins because paclitaxel, which is hydrophobic, was strongly adsorbed on the hydrophobic resin surface. Since high-purity paclitaxel can be obtained in high yield and the precipitation time can be reduced by combining micelle formation with fractional precipitation, this hybrid method is expected to significantly enhance the final purification process.
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