Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Int J Nanomedicine. 2021 Apr 27;16:3059-3071. doi: 10.2147/IJN.S303975. eCollection 2021.
This study aimed to explain the influence of zein nanosphere (ZN NS) formulation on the pharmacotherapeutic profile of PTS in MCF7 cells.
Liquid-liquid phase separation was used to formulate PTS-ZN NSs. The formulations developed were evaluated for particle-size analysis, encapsulation efficiency, and in vitro diffusion. Also, assays of cytotoxicity, uptake, cell-cycle progression, annexin V, apoptotic gene mRNA expression and biochemical assays were carried out.
The PTS-ZN NS formulation selected showed 104.5±6.2 nm, 33.4±1.8 mV, 95.1%±3.6%, and 89.1%±2.65% average particle size, zeta-potential, encapsulation efficiency and in vitro diffusion, respectively. With MCF7 cells, IC was reduced approximately 15-fold, with increased cellular uptake, accumulation in the G/M phase, increased percentage of cells in the pre-G phase, amelioration of early and late apoptosis, raised mRNA expression of CASP3 and CASP7, lower expression of cyclin-CDK1, and enhanced oxidant potential through decreased glutathione reductase (GR) activity, and enhanced reactive oxygen-species generation and lipid-peroxidation products.
PTS-ZN NSs indicated enhanced antiproliferative, proapoptotic, and oxidant potential toward MCF7 cells compared to free PTS. Ameliorated results of nanosized carriers, cellular uptake, and sustained diffusion may contribute to these outcomes.
本研究旨在解释玉米醇溶蛋白纳米球（ZN NS）制剂对 MCF7 细胞中 PTS 药代动力学特征的影响。
采用液-液相分离法制备 PTS-ZN NS。对所开发的制剂进行粒径分析、包封效率和体外扩散评估。同时进行细胞毒性、摄取、细胞周期进程、Annexin V、凋亡基因 mRNA 表达和生化分析检测。
所选择的 PTS-ZN NS 制剂显示出 104.5±6.2nm、33.4±1.8mV、95.1%±3.6%和 89.1%±2.65%的平均粒径、Zeta 电位、包封效率和体外扩散度。在 MCF7 细胞中，IC50 降低了约 15 倍，细胞摄取增加，G/M 期积累增加，G0/G1 期细胞比例增加，早期和晚期凋亡改善，CASP3 和 CASP7 的 mRNA 表达升高，细胞周期蛋白-CDK1 表达降低，通过降低谷胱甘肽还原酶（GR）活性增强氧化应激潜能，增加活性氧（ROS）生成和脂质过氧化产物。
与游离 PTS 相比，PTS-ZN NS 对 MCF7 细胞表现出增强的抗增殖、促凋亡和氧化应激潜能。纳米载体的改善结果、细胞摄取和持续扩散可能有助于这些结果。
