Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
AAPS PharmSciTech. 2022 Jul 1;23(6):183. doi: 10.1208/s12249-022-02332-7.
The present study aimed to engineer a nanoscale lipid-based lymphatic drug delivery system with D-α-Tocopherol polyethylene glycol 1000 succinate to combat the lymphatic metastasis of lung cancer. The nanoscale lipid-based systems including GEF-SLN, GEF-NLC, and GEF-LE were prepared and pharmaceutically characterized. In addition, the most stable formulation (GEF-NLC) was subjected to an in vitro release study. Afterward, the optimized GEF-NLC was engineered with TPGS (GEF-TPGS-NLC) and subjected to in vitro cytotoxicity, and apoptotic studies using the A549 cells line as a surrogate model for lung cancer. The present results revealed that particle size and polydispersity index of freshly prepared formulations were ranging from 198 to 280 nm and 0.106 to 0.240, respectively, with negative zeta potential ranging from - 14 to - 27.6.mV. An in vitro release study showed that sustained drug release was attained from GEF-NLC containing a high concentration of lipid. In addition, GEF-NLC and GEF-TPGS-NLC showed remarkable entrapment efficiency above 89% and exhibited sustained release profiles. Cytotoxicity showed that IC of pure GEF was 11.15 μg/ml which decreased to 7.05 μg/ml for GEF-TPGS-NLC. The apoptotic study revealed that GEF-TPGS-NLC significantly decreased the number of living cells from 67 to 58% when compared with pure GEF. The present results revealed that the nanoscale and lipid composition of the fabricated SLN, NLC, and LE could mediate the lymphatic uptake of GEF to combat the lymphatic tumor metastasis. Particularly, GEF-TPGS-NLC is a promising LDDS to increase the therapeutic outcomes of GEF during the treatment of metastatic lung cancer.
本研究旨在设计一种基于纳米脂质的 D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）纳米递药系统（LDDS），以对抗肺癌的淋巴转移。制备了基于纳米脂质的系统，包括 GEF-SLN、GEF-NLC 和 GEF-LE，并对其进行了药物特征描述。此外，对最稳定的配方（GEF-NLC）进行了体外释放研究。随后，用 TPGS 对优化后的 GEF-NLC 进行了工程化处理（GEF-TPGS-NLC），并采用 A549 细胞系作为肺癌替代模型进行了体外细胞毒性和凋亡研究。结果表明，新制备的制剂的粒径和多分散指数范围分别为 198 至 280nm 和 0.106 至 0.240，ζ 电位为负，范围为-14 至-27.6mV。体外释放研究表明，含有高浓度脂质的 GEF-NLC 能够实现药物的持续释放。此外，GEF-NLC 和 GEF-TPGS-NLC 的包封效率均在 89%以上，表现出持续的释放曲线。细胞毒性实验表明，纯 GEF 的 IC50 为 11.15μg/ml，而 GEF-TPGS-NLC 的 IC50 降低至 7.05μg/ml。凋亡研究表明，与纯 GEF 相比，GEF-TPGS-NLC 可显著降低活细胞数量，从 67%降至 58%。研究结果表明，所制备的 SLN、NLC 和 LE 的纳米尺寸和脂质组成可以介导 GEF 的淋巴摄取，以对抗淋巴肿瘤转移。特别是，GEF-TPGS-NLC 是一种很有前途的 LDDS，可以提高 GEF 在治疗转移性肺癌中的治疗效果。
