Kammoun Ahmed K, Hegazy Maha A, Khedr Alaa, Awan Zuhier Ahmed, Khayat Maan T, Al-Sawahli Majid Mohammad
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia.
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
Pharmaceuticals (Basel). 2022 Jul 24;15(8):916. doi: 10.3390/ph15080916.
This work aimed to enhance the purposing profile of Etodolac (ETD) in Human Hepatocellular Carcinoma (HCC) HepG2 cells using sodium deoxycholate stabilized zein nanospheres (ETD-SDZN NSs). ETD-SDZN NSs were formulated using the nan-precipitation method and were characterized, in particular, in terms of mean particle size, zeta potential, encapsulation efficiency, colloidal stability and bioaccessibility. Estimations of cytotoxicity, cellular uptake, cell cycle progression, Annexin-V staining, mRNA expression of apoptotic genes and oxidative stress evaluations were conducted. The ETD-SDZN NSs selected formula obtained an average particle size of 113.6 ± 7.4 nm, a zeta potential value of 32.7 ± 2.3 mV, an encapsulation efficiency of 93.3 ± 5.2%, enhanced bioaccessibility and significantly reduced IC against HepG2 cells, by approximately 13 times. There was also enhanced cellular uptake, accumulation in G2-M phase and elevated percentage cells in pre-G1 phase, significant elevated mRNA expression of P53, significant reduced expression of Cyclin-dependent kinase 1 (CDK1) and Cyclooxygenase-2 (COX-2) with enhanced oxidative stress by reducing glutathione reductase (GR) level, ameliorated reactive oxygen species (ROS) generation and lipid peroxidation outputs. ETD-SDZN NSs obtained a supreme cell death-inducing profile toward HepG2 cells compared to free ETD. The method of formulation was successful in acquiring the promising profile of ETD in HCC as a therapeutic molecule due to ameliorated cellular uptake, proapoptotic and oxidant potentials.
本研究旨在利用脱氧胆酸钠稳定的玉米醇溶蛋白纳米球（ETD-SDZN NSs）提高依托度酸（ETD）在人肝癌（HCC）HepG2细胞中的应用前景。采用纳米沉淀法制备了ETD-SDZN NSs，并对其进行了表征，特别是在平均粒径、zeta电位、包封率、胶体稳定性和生物可及性方面。进行了细胞毒性、细胞摄取、细胞周期进程、膜联蛋白-V染色、凋亡基因的mRNA表达以及氧化应激评估。所选用配方的ETD-SDZN NSs平均粒径为113.6±7.4 nm，zeta电位值为32.7±2.3 mV，包封率为93.3±5.2%，生物可及性增强，对HepG2细胞的IC显著降低，约为原来的13倍。细胞摄取也有所增强，在G2-M期积累，G1期前细胞百分比升高，P53的mRNA表达显著升高，细胞周期蛋白依赖性激酶1（CDK1）和环氧化酶-2（COX-2）的表达显著降低，通过降低谷胱甘肽还原酶（GR）水平增强氧化应激，改善活性氧（ROS）生成和脂质过氧化产物。与游离ETD相比，ETD-SDZN NSs对HepG2细胞具有更强的诱导细胞死亡的作用。由于改善了细胞摄取、促凋亡和氧化潜力，该制备方法成功地使ETD在肝癌中作为治疗分子展现出良好的应用前景。
