Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
Micro & Nanomedecines Translationnelles - MINT, UNIV Angers, INSERM U1066, CNRS UMR 6021, UBL Université Bretagne Loire, Angers, France.
Int J Pharm. 2019 Mar 25;559:220-227. doi: 10.1016/j.ijpharm.2019.01.042. Epub 2019 Jan 28.
Lauroyl-gemcitabine lipid nanocapsules (GemC-LNC) hydrogel, administered intratumorally or perisurgically in the tumor resection cavity, increases animal survival in several orthotopic GBM models. We hypothesized that GemC-LNC can be used as nanodelivery platform for other drugs, to obtain a combined local therapeutic approach for GBM. Paclitaxel (PTX) was selected as a model molecule and PTX-GemC-LNC formulation was evaluated in terms of physicochemical and mechanical properties. The PTX-GemC-LNC hydrogel stability and drug release were evaluated over time showing no significant differences compared to GemC-LNC. The drug combination was evaluated on several GBM cell lines showing increased cytotoxic activity compared to the original formulation and synergy between PTX and GemC. Our results suggest that GemC-LNC hydrogel can be used as nanodelivery platform for dual drug delivery to encapsulate active agents with different mechanisms of action to achieve a better antitumor efficacy against GBM or other solid tumors.
月桂酰基吉西他滨脂质纳米胶囊（GemC-LNC）水凝胶，通过肿瘤内或肿瘤切除腔周围局部给药，可提高几种原位 GBM 模型动物的存活率。我们假设 GemC-LNC 可以用作其他药物的纳米递送平台，以获得针对 GBM 的联合局部治疗方法。紫杉醇（PTX）被选为模型分子，并评估了 PTX-GemC-LNC 制剂在物理化学和机械性能方面的表现。PTX-GemC-LNC 水凝胶的稳定性和药物释放随时间的变化与 GemC-LNC 相比没有显著差异。该药物组合在几种 GBM 细胞系中的评估显示，与原始制剂相比，细胞毒性活性增加，并且 PTX 和 GemC 之间存在协同作用。我们的研究结果表明，GemC-LNC 水凝胶可用作双药物递送的纳米载体，封装具有不同作用机制的活性剂，以针对 GBM 或其他实体瘤实现更好的抗肿瘤疗效。
