生物可降解聚合体递送吉西他滨到Panc-1细胞。

Nimil Sood, Walter T Jenkins, Xiang-Yang Yang, Nikesh N Shah, Joshua S Katz, Cameron J Koch, Paul R Frail, Michael J Therien, Daniel A Hammer, Sydney M Evans
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引用次数: 5

摘要

传统的抗癌化疗往往毒副作用大,生物利用度差,治疗指数低。化疗药物的靶向和控制释放可以提高药物的生物利用度,减轻不良副作用,提高治疗指数。在这里,我们报告了一种基于聚合物的系统,将吉西他滨输送到体外的Panc-1细胞。聚合体由生物相容性和完全可生物降解的聚合物聚环氧乙烷-聚己内酯,PEO-PCL自组装而成。结果表明,我们可以将吉西他滨包封在稳定的200 nm囊泡内,负载效率为10%。在生理ph下2天后,这些囊泡显示出吉西他滨的控释,释放量为60%。在体外处理Panc-1细胞后,用荧光标记的聚合体验证了囊泡的内化。用不同浓度的未包封的吉西他滨(FreeGem)和聚合物包封的吉西他滨(PolyGem)处理Panc-1细胞48小时,进行克隆测定以确定细胞存活率。1 μM PolyGem对肿瘤细胞的毒性与1 μM FreeGem相当,并观察到1 log细胞死亡。这些研究表明,进一步研究以聚合物为基础的药物制剂是胰腺癌化疗的必要条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.

Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.

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来源期刊
Journal of Pharmaceutics
Journal of Pharmaceutics PHARMACOLOGY & PHARMACY-
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