Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India.
School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India.
ACS Appl Bio Mater. 2024 Oct 21;7(10):6832-6846. doi: 10.1021/acsabm.4c00958. Epub 2024 Sep 27.
The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC value of 12.5 μg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.
本研究聚焦于载有吉西他滨(GEM)和表没食子儿茶素没食子酸酯(EGCG)的固体脂质纳米粒(SLNs)的配方、表征和评估,用于肺癌治疗。采用 2 水平 3 因素析因设计优化 SLNs 制备中的各种工艺参数。发现 GEM-EGCG SLNs 的平均粒径和多分散指数(PDI)分别为 122.8±8.02nm 和 0.1738±0.02。药物载量和释放研究表明 GEM-EGCG SLNs 具有缓释行为,释放动力学通过 Higuchi 模型得到证实。通过 MTT 测定法评估细胞活力和抗癌活性,确定 GEM-EGCG SLNs 对 A549 细胞系(肺癌上皮细胞)的 IC 值为 12.5μg/mL。这些 SLNs 能够进入细胞的细胞核,可能是由于其粒径较小,并且能够有效地杀死癌细胞。此外,还通过 FACS 研究了 A549 细胞中 ROS 产生介导的细胞凋亡。研究发现 GEM-EGCG SLNs 在 3 个月内稳定。体内研究表明,与纯药物相比,GEM-EGCG SLNs 在肺部的药物分布更好,药代动力学特征得到改善。总的来说,这些结果表明,将 GEM 和 EGCG 结合到生物相容性 SLNs 中,产生了协同的抗肿瘤潜力,并提高了两种药物的生物利用度,使其成为一种有前途的针对肺癌的抗癌治疗方案。