Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.
King Institute of Preventive Medicine & Research, Chennai 600 032, Tamil Nadu, India.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109716. doi: 10.1016/j.msec.2019.05.001. Epub 2019 May 2.
Improved therapeutic effects can be achieved by the delivery of combination of drugs through multifunctional cell targeted nanocarrier systems. The present investigation reports the preparation of Poly (D,L-lactic-co-glycolic acid) (PLGA) nanospheres loaded with the novel combination such as Rutin (R) and Benzamide (B) as drugs using water-oil-water (w/o/w) emulsion method. Dual drug loaded PLGA nanospheres (R/B@PLGA) were stabilized by poly (vinyl alcohol) (PVA) coating and characterized in terms of morphology, size, surface charge, and structural chemistry by Scanning electron microscopy (SEM), Dynamic light scattering (DLS), Zeta potential analysis, UV-vis and Fourier transform infrared (FT-IR) spectroscopy. The inhibitory effects of rutin and benzamide on MDA-MB-231 (triple negative breast cancer-TNBC) cells using the drug loaded PLGA nanospheres as well as their non-toxic features were evaluated in vivo. The anticancer activity of the R/B@PLGA nanospheres through cell cycle disruption and apoptotic induction was assessed in vitro by flow cytometry analysis. Further, the in vitro antioxidant capacity, pH-based drug release and hemocompatible property were also investigated. It was shown that the R/B@PLGA nanospheres lacked genotoxic potential and they did not alter the antioxidant enzyme activities and histological features of zebrafish. Hence, this dual drug delivery system (DDS) not only actively targets multidrug-resistance (MDR) associated phenotype but also improves the therapeutic efficiency by its non-toxic nature towards enhanced cancer cell focused delivery and sustained release of therapeutic agents.
通过多功能细胞靶向纳米载体系统递送药物组合可以实现更好的治疗效果。本研究报告了使用水包油包水（w/o/w）乳液法制备载有新型组合药物如芦丁（R）和苯甲酰胺（B）的聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米球。双载药 PLGA 纳米球（R/B@PLGA）通过聚（聚乙烯醇）（PVA）涂层稳定，并通过扫描电子显微镜（SEM）、动态光散射（DLS）、Zeta 电位分析、紫外可见分光光度法和傅里叶变换红外（FT-IR）光谱对其形态、大小、表面电荷和结构化学进行了表征。使用载药 PLGA 纳米球评估了芦丁和苯甲酰胺对 MDA-MB-231（三阴性乳腺癌-TNBC）细胞的抑制作用及其无毒特性。通过流式细胞术分析评估了 R/B@PLGA 纳米球通过细胞周期破坏和诱导凋亡的体外抗癌活性。此外，还研究了体外抗氧化能力、基于 pH 的药物释放和血液相容性。结果表明，R/B@PLGA 纳米球没有遗传毒性，并且不会改变斑马鱼的抗氧化酶活性和组织学特征。因此，这种双药物递送系统（DDS）不仅可以主动靶向多药耐药（MDR）相关表型，还可以通过其对增强的癌细胞靶向递送和治疗剂的持续释放的无毒性质来提高治疗效率。
