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基于纳米的药物传递系统在传递和靶向微管结合剂,纳布啡用于癌细胞中的应用。

Implications of nanoscale based drug delivery systems in delivery and targeting tubulin binding agent, noscapine in cancer cells.

机构信息

Dr. B.R Ambedkar Centre for Biomedical Research, University of Delhi, Delhi-110007, India.

出版信息

Curr Drug Metab. 2012 Dec;13(10):1476-83. doi: 10.2174/138920012803762756.

DOI:10.2174/138920012803762756
PMID:22571485
Abstract

Noscapine, a tubulin binding anticancer agent undergoing Phase I/II clinical trials, inhibits tumor growth in nude mice bearing human xenografts of breast, lung, ovarian, brain, and prostrate origin. The analogues of noscapine like 9-bromonoscapine (EM011) are 5 to 10-fold more active than parent compound, noscapine. Noscapinoids inhibit the proliferation of cancer cells that are resistant to paclitaxel and epothilone. Noscapine also potentiated the anticancer activity of doxorubicin in a synergistic manner against triple negative breast cancer (TNBC). However, physicochemical and pharmacokinetic (ED50˜300-600 mg/kg bodyweight) limitations of noscapine present hurdle in development of commercial anticancer formulations. Therefore, objectives of the present review are to summarize the chemotherapeutic potential of noscapine and implications of nanoscale based drug delivery systems in enhancing the therapeutic efficacy of noscapine in cancer cells. We have constructed noscapine-enveloped gelatin nanoparticles, NPs and poly (ethylene glycol) grafted gelatin NPs as well as inclusion complex of noscapine in β-cyclodextrin (β-CD) and evaluated their physicochemical characteristics. The Fe3O4 NPs were also used to incorporate noscapine in its polymeric nanomatrix system where molecular weight of the polymer governed the encapsulation efficiency of drug. The enhanced noscapine delivery using μPAR-targeted optical-MR imaging trackable NPs offer a great potential for image directed targeted delivery of noscapine. Human Serum Albumin NPs (150-300 nm) as efficient noscapine drug delivery systems have also been developed for potential use in breast cancer.

摘要

北美黄连碱,一种正在进行 I/II 期临床试验的微管结合抗癌药物,可抑制荷人异种移植乳腺癌、肺癌、卵巢癌、脑癌和前列腺癌裸鼠肿瘤生长。北美黄连碱类似物,如 9-溴北美黄连碱 (EM011),比母体化合物北美黄连碱活性高 5-10 倍。北美黄连碱类抑制对紫杉醇和埃坡霉素耐药的癌细胞增殖。北美黄连碱还以协同方式增强多柔比星对三阴性乳腺癌 (TNBC) 的抗癌活性。然而,北美黄连碱的物理化学和药代动力学(ED50˜300-600mg/kg 体重)限制了其在商业抗癌制剂开发中的应用。因此,本综述的目的是总结北美黄连碱的化疗潜力,并探讨基于纳米技术的药物传递系统对增强北美黄连碱在癌细胞中的治疗效果的意义。我们构建了北美黄连碱包被的明胶纳米粒、聚乙二醇接枝明胶纳米粒以及北美黄连碱包封于β-环糊精(β-CD)中的包合物,并对其理化性质进行了评价。还使用 Fe3O4 NPs 将北美黄连碱包埋在其聚合物纳米基质系统中,其中聚合物的分子量决定了药物的包封效率。通过靶向 μPAR 的光学-MR 成像可追踪纳米粒增强了北美黄连碱的递送,为北美黄连碱的靶向递药提供了很大的潜力。我们还开发了 150-300nm 的人血清白蛋白纳米粒(HSA-NPs)作为有效的北美黄连碱药物传递系统,有望用于乳腺癌的治疗。

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