Dual drug delivery of curcumin and niclosamide using PLGA nanoparticles for improved therapeutic effect on breast cancer cells
Dual drug delivery of curcumin and niclosamide using PLGA nanoparticles for improved therapeutic effect on breast cancer cells
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DOI：
10.1007/s10965-020-02092-7
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发表时间：
2020-05-05
影响因子：
2.8
通讯作者：
Bandyopadhyaya, Rajdip
中科院分区：
文献类型：
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作者：
Prabhuraj, R. S.;Bomb, Kartik;Bandyopadhyaya, Rajdip
一些有效的化学预防剂如姜黄素和氯硝柳胺已经显示出有希望的癌症活性，尽管具有生物利用度差的缺点。为了提高这些药物在癌症治疗中的效用，我们已经将姜黄素和氯硝柳胺封装在聚（乳酸-共-乙交酯）（PLGA）纳米颗粒中，在聚（乙烯醇）的存在下，使用纳米沉淀法。我们成功地合成了球形PLGA纳米颗粒，无论是与每一个单一的药物单独或与两种药物在一起，双载药样品。FTIR光谱证实了姜黄素和氯硝柳胺在PLGA纳米颗粒中的成功负载。当单独装载时，姜黄素和氯硝柳胺的包封率分别为48.15%和70.27%;当同时进行双药物包封时，姜黄素和氯硝柳胺的包封率分别增加到58.09%和85.36%。体外药物释放表明，根据需要，与正常健康细胞的pH 7.4（对于这两种相同的药物，分别为25.70%和60.92%）相比，在癌细胞的酸性pH 6.0下释放的药物量要高得多（对于姜黄素和氯硝柳胺，分别为86.01%和95.04%）。MTT法显示，双药物负载的PLGA纳米粒表现出更高的抗癌效果，相比，在DMSO中的两种药物的裸混合物（没有PLGA）。因此，PLGA纳米粒可作为有效载体将两种疏水性药物递送至MDA-MB-231乳腺癌细胞，具有上级抗癌效果。
A number of potent chemopreventives like curcumin and niclosamide have shown promising activities in cancer, although having the drawback of poor bioavailability. To improve the utility of these drugs in cancer therapy, we have encapsulated curcumin and niclosamide in poly(lactic-co-glycolide) (PLGA) nanoparticles, in the presence of poly(vinyl alcohol), using the nanoprecipitation method. We successfully synthesised spherical PLGA nanoparticles, either with each of the single drug individually or with both drugs together, for dual drug loaded samples. FTIR spectroscopy confirmed the successful loading of curcumin and niclosamide in PLGA nanoparticles. The encapsulation efficiency was 48.15% and 70.27% for curcumin and niclosamide, respectively, when loaded individually; which increased to 58.09% for curcumin and 85.36% for niclosamide, with simultaneous dual drug encapsulation. In vitro drug release showed that, as required, a much higher amount of drug released at the acidic pH 6.0 of cancer cells (86.01%, 95.04%, for curcumin and niclosamide, respectively), compared to normal, healthy cell's pH of 7.4 (25.70% and 60.92% for these two same drugs). MTT assay revealed that dual-drug loaded PLGA nanoparticles exhibited a higher anticancer effect, compared to a bare mixture of two drugs in DMSO (having no PLGA). Therefore, PLGA nanoparticles can be used as an effective carrier to deliver the two hydrophobic drugs to MDA-MB-231 breast cancer cells, for a superior anticancer effect.