Bastiancich C, Vanvarenberg K, Ucakar B, Pitorre M, Bastiat G, Lagarce F, Préat V, Danhier F
Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
LUNAM Université, UMR-S1066, Angers F-49933, France; INSERM U 1066, Micro et Nanomédecines Biomimétiques - MINT, Angers F-49933, France.
J Control Release. 2016 Mar 10;225:283-93. doi: 10.1016/j.jconrel.2016.01.054. Epub 2016 Jan 30.
The local delivery of chemotherapeutic agents is a very promising strategy for the treatment of glioblastoma (GBM). Gemcitabine is a chemotherapeutic agent that has a different mechanism of action compared to alkylating agents and shows excellent radio-sensitizing properties. So, we developed an injectable gel-like nanodelivery system consisting in lipid nanocapsules loaded with anticancer prodrug lauroyl-gemcitabine (GemC12-LNC) in order to obtain a sustained and local delivery of this drug in the brain. In this study, the GemC12-LNC has been formulated and characterized and the viscoelastic properties of the hydrogel were evaluated after extrusion from 30G needles. This system showed a sustained and prolonged in vitro release of the drug over one month. GemC12 and the GemC12-LNC have shown increased in vitro cytotoxic activity on U-87 MG glioma cells compared to the parent hydrophilic drug. The GemC12-LNC hydrogel reduced significantly the size of a subcutaneous human GBM tumor model compared to the drug and short-term tolerability studies showed that this system is suitable for local treatment in the brain. In conclusion, this proof-of-concept study demonstrated the feasibility, safety and efficiency of the injectable GemC12-LNC hydrogel for the local treatment of GBM.
局部递送化疗药物是治疗胶质母细胞瘤（GBM）非常有前景的策略。吉西他滨是一种化疗药物，其作用机制与烷化剂不同，具有出色的放射增敏特性。因此，我们开发了一种可注射的凝胶状纳米递送系统，该系统由负载抗癌前药月桂酰吉西他滨（GemC12-LNC）的脂质纳米囊组成，以便在脑中实现该药物的持续局部递送。在本研究中，已对GemC12-LNC进行了配方设计和表征，并在从30G针头挤出后评估了水凝胶的粘弹性。该系统在体外显示出药物持续释放超过一个月。与亲水性母体药物相比，GemC12和GemC12-LNC对U-87 MG胶质瘤细胞的体外细胞毒性活性有所增加。与药物相比，GemC12-LNC水凝胶显著减小了皮下人GBM肿瘤模型的大小，短期耐受性研究表明该系统适用于脑部局部治疗。总之，这项概念验证研究证明了可注射的GemC12-LNC水凝胶用于GBM局部治疗的可行性、安全性和有效性。
