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Capsular Perstraction as a Novel Methodology for the Recovery and Purification of Geldanamycin

机译:胶囊包膜作为格尔德霉素回收和纯化的新方法

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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 x 10~(-6) m/s was obtained for the highest agitation speed (400 rpm), which was considerable greater compared to the value of 0.88 x 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.
机译:分子复合物“热休克蛋白90”由于其作为伴侣蛋白对参与癌症发展的蛋白表现出的能力而成为近来抗癌药物的新靶标。格尔德霉素以高亲和力与该复合物结合并阻止其正确执行,从而导致肿瘤破坏。这项研究的目的是研究将液体核心微胶囊作为一种新技术(称为“胶囊渗透”)从培养基中回收和纯化格尔德霉素的可行性。结果表明,该方法如何能够仅使用1%的液芯体积与培养基的比率从培养基中快速提取> 70%的格尔德霉素。检查了最佳的去除条件,包括搅拌速度,微囊尺寸和膜厚度,结果表明微囊周围停滞的水膜是主要的传质阻力。对于最高的搅拌速度(400 rpm),获得的质量传质系数为5.66 x 10〜(-6)m / s,相比于实现的0.88 x 10〜(-6)m / s的值,传质系数大得多。最低转速为100 rpm。还检查了从微胶囊中去除格尔德霉素的情况,以全面研究此类颗粒在原位产物回收中的潜力,并证明了该方法可如何用作通过溶剂萃取和结晶纯化化合物(> 99%)的简单机制。这项工作的结果证明了囊膜渗透作为从培养环境中回收和纯化格尔德霉素的方法学的新颖用途。

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