Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.
Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran.
Drug Dev Ind Pharm. 2020 Sep;46(9):1535-1549. doi: 10.1080/03639045.2020.1810269. Epub 2020 Aug 28.
The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells.
Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity .
Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells.
Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes.
The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.
本研究旨在使用纳米脂质体制剂将辛伐他汀作为一种难溶于水的药物递送到乳腺癌细胞中。
我们的研究专注于与具有显著生物活性的水溶性差的药物相关的问题。
制备并考察了不同辛伐他汀纳米脂质体的形态、粒径、包封率（EE）和释放动力学。采用实时定量 PCR 和流式细胞术评估了辛伐他汀的抗增殖活性和作用机制。此外，还采用共聚焦显微镜分析了载辛伐他汀纳米脂质体向癌细胞的摄取情况。
最佳制剂的粒径、多分散指数（PDI）和 EE 分别为 164.8nm、0.232 和 97%。制得的辛伐他汀呈球形，72h 后药物呈现缓慢释放特征。稳定性数据表明，与 25°C 相比，4°C 时平均粒径和 PDI 增加较小。共聚焦显微镜显示药物负载的纳米脂质体在癌细胞中的定位。MTT 试验表明，游离药物和载药纳米脂质体均对乳腺癌细胞（MDA-MB-231 细胞）表现出剂量依赖性细胞毒性。流式细胞术和 qPCR 分析表明，载药纳米脂质体通过调节凋亡和抗凋亡基因对癌细胞发挥细胞毒性作用。
与游离药物相比，所制备的辛伐他汀纳米脂质体具有更好的物理化学和生物学性质。我们的研究表明，纳米脂质体递药系统可被视为将难溶性药物递送到癌细胞的一种有前途的策略。
