Capsular perstraction as a novel methodology for the recovery and purification of geldanamycin

Abstract

The molecular complex "Heat shock protein 90" has become a novel target for anticancer drugs in recent times on account of its ability to perform as a chaperone toward proteins involved in cancer progression. The geldanamycin binds to this complex with high affinity and prevents it from performing correctly, which results in tumor destruction. The aim of this study was to investigate the feasibility of applying liquid-core microcapsules as a novel technique (termed "capsular perstraction"), for the recovery and purification of geldanamycin from culture media. Results demonstrated how this procedure was capable of rapidly extracting >70% of geldanamycin from culture media using a liquid-core volume to medium ratio of only 1%. Optimum conditions for removal, including agitation speed, microcapsule size, and membrane thickness were examined, and it was shown how the stagnant aqueous film around the microcapsules was the main resistance to mass transfer. A volumetric mass transfer coefficient of 5.66×10(-6) m/s was obtained for the highest agitation speed (400 rpm), which was considerable greater compared to the value of 0.88×10(-6) m/s achieved for the lowest speed of 100 rpm. Removal of geldanamycin from microcapsules was also examined to fully investigate the potential of such particles for in situ product recovery, and it was demonstrated how the methodology can be used as a simple mechanism for purifying the compound (>99%) through solvent extraction and crystallization. The results of this work demonstrate the novel use of capsular perstraction as a methodology for the recovery and purification of geldanamycin from culture environments.