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纳米制剂萘普生及其他非甾体抗炎药的异常抗白血病活性

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs.

作者信息

Kumar Raj, Siril Prem Felix, Javid Farideh

机构信息

School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005, India; Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005, India.

School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005, India; Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005, India.

出版信息

Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:1335-44. doi: 10.1016/j.msec.2016.08.024. Epub 2016 Aug 9.

Abstract

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug.

摘要

非甾体抗炎药(NSAIDs)是全球使用最广泛的药物。有趣的是,其中许多药物也具有显著的抗癌特性。然而,某些NSAIDs的水溶性较差限制了它们在癌症治疗中的应用。将这类药物制成纳米颗粒有助于提高其溶解度,这也可能增强抗癌活性。此外,通过提高NSAIDs的溶解度和生物利用度,可以将其过量用药及伴随的副作用降至最低。本文报道了使用一种新型蒸发辅助溶剂 - 反溶剂相互作用(EASAI)方法成功制备三种NSAIDs(布洛芬(IBP)、酮洛芬(KP)和萘普生(NAP))的纳米制剂。使用三种水溶性且生物相容的聚合物:聚乙烯吡咯烷酮(PVP)、聚乙烯醇(PVA)和羟丙基甲基纤维素(HPMC)来稳定药物纳米颗粒。使用动态光散射和场发射扫描电子显微镜(FESEM)成像对平均尺寸低于30nm的球形颗粒进行了全面表征。该纳米制剂使NSAIDs的溶解度提高了10至15倍,并显著增强了其体外药物释放曲线。对纳米制剂化的NSAIDs针对五种不同癌细胞系进行了抗癌筛选,这些细胞系包括MCF - 7(人乳腺癌细胞系)、MIA - PA - CA - 2(人胰腺癌细胞系)、HT - 29(人结肠癌细胞系)、Jurkat(人白血病细胞系)和A2780(人卵巢癌细胞系)。所有纳米制剂化样品对白血病癌细胞系均显示出增强的抗癌活性,其中NAP - PVP表现出最高的抗癌活性。NAP - PVP的抗白血病活性是标准抗癌药物阿霉素的两倍多。

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