Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Ajmer 305817, India.
Department of Biotechnology, IIS (Deemed to be University), Jaipur Rajasthan 302020, India.
Molecules. 2020 Sep 16;25(18):4243. doi: 10.3390/molecules25184243.
Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8-145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from -17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.
联合使用化学性质不同的药物已成为提高抗癌治疗效果的一种有前途的策略之一。在本研究中,制备了聚(乳酸-共-乙醇酸)(PLGA)纳米粒与基于聚乙烯亚胺(PEI)的共递药系统静电偶联的多柔比星和紫杉醇(PLGA-PEI-EPI-PTX NPs)。PLGA-PEI-EPI-PTX NPs 通过 DLS 测量表现出单分散的粒径分布,平均粒径为 240.93 ± 12.70nm,通过 AFM 测量为 70.8-145nm。从 -17.45 ± 2.15mV 到 41.95 ± 0.65mV 的 zeta 电位进一步证实了 PLGA 纳米粒的胶体稳定性和 PEI 修饰。通过分光光度法进行了纳米粒的包封和载药效率以及体外释放。PLGA-PEI-EPI-PTX NPs 的傅里叶变换红外(FTIR)分析表明聚合物 PLGA 和 PEI 之间存在酰胺部分。通过划痕愈合试验也证实了纳米粒对细胞迁移的影响。MTT 试验表明,PLGA-PEI-EPI-PTX NPs 表现出相当的抗癌潜力,优于原始药物。此外,通过 Western blot 分析 p53 蛋白表达显示出增强的表达。这项研究表明,PLGA-PEI-EPI-PTX NPs 的联合治疗代表了一种潜在的方法,并可能为未来的肺癌患者带来临床益处。