Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India.
Department of Pharmaceutical Sciences and Natural Products, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India.
Pharm Res. 2019 Aug 16;36(10):149. doi: 10.1007/s11095-019-2677-5.
Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles.
Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP).
Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC of 1.94 ± 0.22 and 1.02 ± 0.36 μM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration.
The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies.
组合方法可有益于癌症治疗并促进患者康复。天然和合成抗癌药物的共递药不仅有助于实现更好的抗癌效果，还能确定毒性。本研究旨在通过聚（乳酸-共-乙醇酸）（PLGA）纳米粒利用共轭/包封策略共递药盐酸小檗碱（天然来源）和阿霉素（合成来源）。
阿霉素通过碳二亚胺化学有效地共轭到 PLGA 上，并用 PLGA-阿霉素缀合物（PDC）包封盐酸小檗碱（PDBNP）。
对 MDA-MB-231 和 T47D 乳腺癌细胞系的显著抗增殖作用，IC 为 1.94±0.22 和 1.02±0.36μM，明显优于生物活性物质（p<0.05）。ROS 研究表明，PDBNP 以剂量依赖性方式在 MDA-MB-231 细胞系中略微增加活性氧（ROS）模式，而在 T47D 细胞中，ROS 没有明显变化。PDBNP 显示出线粒体膜通透性的显著改变（去极化）和细胞周期在亚 G1 期的停滞，而 Annexin V/PI 测定随后通过共聚焦显微镜导致细胞死亡模式是由于 MDA-MB-231 细胞的坏死。在 Sprague Dawley 大鼠中的体内研究表明，半衰期增加了近 14 倍，血浆药物浓度显著增加。
基于 PLGA 的阿霉素和盐酸小檗碱共递药的整体方法见证了协同作用，并通过初步毒性研究证明了毒性降低。
