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Development of bioerodible, short-term controlled-release microcapsules for cancer chemotherapy

开发用于癌症化疗的生物可蚀性短期控释微胶囊

基本信息

批准号：
09672204
负责人：
YAMAOKA Yumiko
金额：
$ 1.79万
依托单位：
Faculty of Pharmaceutical Sciences, Kobe Gakuin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

Lecithin microcapsules (LMCs) specified by short-term delayed drug-release and bioerosion were developed for intraarteial chemoembolization therapy of cancer. An air suspension coating process was employed to microencapsulate a lactose core with a layer of drug, soybean lecithin (SL), cholesterol (CH), stearic acid (SA) and polyvinylpyrrolidone (PVP) and a coat of SL, CH, SA and PVP. The particle size drug content of the LMCs thus prepared could be varied in the range of 30-200 μm and few to 30%, respectively. By changing the weight rations of four components of the LMCs coat, bioerosion and short-term drug-release properties were also found to be widely changeable. The estimated phase diagram of the SL-CH-SA system incorporating 42% PVP indicated that the mechanisms of drug-release and bioerosion were closely related to the phase-separation behavior of each component in the coat. Small-scale production of the LMCs by the air suspension coating process was also established based on a novel dilution method, taking into consideration of the tailor-made treatment for individual patients in preclinical use where various types of microcapsules with versatile functions were required. This method provided microcapsules with 106-149 μm in size and 30% in drug content by using only 1 g of an anticancer drug (adriamycin (ADR)). The ADR-containing LMCs also demonstrated short-term delayed release of ADR with a lagtime of few to ten minutes while they could be completely eroded within 30 min in human plasma in vitro. These properties were achieved even in vivo studies where the ADR-LMCs were intraarterially injected to hepatic artery of rats, suggesting that the ADR-LMCs may induce transient arterial-embolization and thereby enhance the pharmacological effect of ADR released in the embolic arteries. These results demonstrate that the LMCs developed in this study will be a promising class of drug carriers for intraarterial chemoembolization therapy of cancer.

卵磷脂微胶囊具有短期缓释和生物侵蚀特性，可用于动脉内化疗栓塞治疗癌症。采用空气悬浮包覆工艺，在乳糖核芯上包覆药物、大豆卵磷脂（SL）、胆固醇（CH）、硬脂酸（SA）和聚乙烯吡咯烷酮（PVP），包覆SL、CH、SA和PVP。所制备的lmc的粒径和药物含量分别在30 ~ 200 μm和30% ~ 30%之间变化。通过改变四种成分的重量比，生物侵蚀和短期药物释放性能也会发生很大的变化。添加42% PVP的SL-CH-SA体系的相图表明，药物释放和生物侵蚀的机制与包被中各组分的相分离行为密切相关。考虑到临床前患者需要不同类型、功能多样的微胶囊，基于一种新型稀释法，采用空气悬浮包衣工艺建立了lmc的小规模生产。该方法仅使用1 g抗癌药阿霉素（ADR），制备出粒径为106 ~ 149 μm、药物含量为30%的微胶囊。含有ADR的lmc还表现出ADR的短期延迟释放，滞后时间为几至十分钟，而在体外人血浆中可在30分钟内完全被侵蚀。即使在大鼠肝动脉内注射ADR- lmcs的体内研究中也获得了这些特性，这表明ADR- lmcs可能诱导短暂的动脉栓塞，从而增强ADR在栓塞动脉中释放的药理作用。这些结果表明，本研究开发的lmc将是一类有前景的动脉内化疗栓塞治疗癌症的药物载体。