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首页> 外文期刊>Colloids and Surfaces, B. Biointerfaces >Improved chemotherapeutic efficacy against resistant human breast cancer cells with co-delivery of Docetaxel and Thymoquinone by Chitosan grafted lipid nanocapsules: Formulation optimization, in vitro and in vivo studies
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Improved chemotherapeutic efficacy against resistant human breast cancer cells with co-delivery of Docetaxel and Thymoquinone by Chitosan grafted lipid nanocapsules: Formulation optimization, in vitro and in vivo studies

机译:通过壳聚糖接枝脂质纳米胶囊加入多西紫杉醇和胸腺酮的共同递送抗性人乳腺癌细胞的化学治疗疗效:制剂优化,体外和体内研究

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摘要

In recent years, multi-targeted chemotherapeutic combinations have received considerable attention in solid tumor chemotherapy. Here, we optimized low-molecular-weight chitosan (CS)-grafted lipid nanocapsules (LNCs, referred to as CLNCs) for the co-delivery of docetaxel (DTX) and thymoquinone (THQ) to treat drug-resistant breast cancer. We first screened size reduction techniques (homogenization vs ultrasonication), and then the 3(3)-Box-Behnken design was employed to determine optimal conditions of the final LNCs with the desired quality attributes. Uncoated LNCs had a particle size of 141.7 +/- 2.8 nm (Polydispersity index, PdI: 0.17 +/- 0.02) with entrapment efficiency (%EE) of 66.1 +/- 3.5 % and 85.3 +/- 3.1 % for DTX and THQ, respectively. The CS functionalization of LNCs improved the uptake and endosomal escape effect, and led to a significantly higher cytotoxicity against MCF-7 and triple-negative (MDA-MB-231) breast cancer cells. Furthermore, an enhanced antiangiogenic effect was observed with DTX- and THQ-carrying CLNCs in the Chick embryo chorioallantoic membrane (CAM) assay.
机译:近年来,多目标化学治疗组合在实体肿瘤化疗中得到了相当大的关注。这里,我们优化了用于Cocetaxel(DTX)和胸腺酮(THQ)的共递送的低分子量壳聚糖(CS) - 移植脂质纳米粉刺(LNC,称为ClNC),以治疗耐药乳腺癌。我们首先筛选尺寸减小技术(均质化VS超声波),然后采用3(3)箱-Bhnken设计来确定最终LNC的最佳条件,具有所需的质量属性。未涂覆的LNC具有141.7 +/- 2.8nm(多分散指数,PDI:0.17 +/- 0.02)的粒径,含有66.1 +/- 3.5%和85.3 +/- 3.1%的血迹效率(%ee),而DTX和THQ , 分别。 LNC的CS官能化改善摄取和内体逃逸效应,并导致对MCF-7和三阴性(MDA-MB-231)乳腺癌细胞的显着更高的细胞毒性。此外,在鸡胚胚胎血管膜(CAM)测定中,用DTX和CHQ携带的CLNC观察到增强的抗血管生成效果。

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