Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran.
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
J Pharm Sci. 2024 Nov;113(11):3362-3374. doi: 10.1016/j.xphs.2024.09.010. Epub 2024 Sep 12.
Docetaxel (DTX) is one of the most potent anticancer drugs but its extensive side effects necessitate innovative formulations. In this study, we aimed to investigate the expression pattern of apoptotic proteins, cell cycle arrest, and apoptosis induction after treatment with encapsulated DTX in alginate-chitosan nanoparticles in both breast cancer cells (MCF-7) and peripheral blood mononuclear cells (PBMCs). The characterization of the nanoparticles revealed a spherical shape with a size <50 nm, a hydrodynamic diameter of 200 nm, a Polydispersity Index of 0.5, and an encapsulation efficiency of 98.75 %. The free drug was released completely within 11 h while encapsulated DTX was released only 34 % in 96 h. The encapsulated drug indicated higher cytotoxicity on MCF-7 cells and the half inhibitory concentration (IC) value was 2 µg/ml after 72 h. Quantitative real-time PCR demonstrated a significant increase in cell death as the expression of apoptosis regulatory protein (Bcl-2) was downregulated with no impact on Bax in the MCF-7 cells. A notable decrease in the expression pattern of pro-inflammatory cytokine (IL-1β) in PBMCs indicated less inflammation induction. Flow cytometry analysis revealed that the newly formulated drug induced less opoptosis in PBMCs than the free DTX. Cell cycle arrest in the sub-G phase was observed for the free drug while the encapsulated drug exhibited no significant changes. Our results suggest the high toxicity of the formulated drug in contrast to the free DTX on the MCF-7 cell line, minimal blood cell side effects, and no inflammation positioning it as a promising alternative to free docetaxel.
多西紫杉醇(DTX)是最有效的抗癌药物之一,但广泛的副作用需要创新的制剂。在这项研究中,我们旨在研究用海藻酸钠-壳聚糖纳米粒包裹 DTX 处理后乳腺癌细胞(MCF-7)和外周血单个核细胞(PBMC)中凋亡蛋白表达模式、细胞周期停滞和凋亡诱导。纳米粒的特征分析显示其为 <50nm 的球形,粒径为 200nm,多分散指数为 0.5,包封效率为 98.75%。游离药物在 11 小时内完全释放,而包裹的 DTX 在 96 小时内仅释放 34%。包裹的药物对 MCF-7 细胞表现出更高的细胞毒性,72 小时后半抑制浓度(IC)值为 2μg/ml。实时定量 PCR 表明,细胞死亡明显增加,凋亡调节蛋白(Bcl-2)的表达下调,而 Bax 没有影响。MCF-7 细胞中促炎细胞因子(IL-1β)的表达模式明显下降,表明炎症诱导减少。流式细胞术分析表明,新制剂药物在 PBMC 中诱导的细胞凋亡少于游离 DTX。游离药物观察到细胞周期在 sub-G 期停滞,而包裹药物没有明显变化。我们的结果表明,与游离 DTX 相比,新制剂药物在 MCF-7 细胞系上具有更高的毒性,对血细胞的副作用最小,无炎症,这使其成为游离多西紫杉醇的一种有前途的替代药物。