Glioblastoma (GBM) treatment includes, when possible, surgical resection of the tumor followed by radiotherapy and oral chemotherapy with temozolomide, however recurrences quickly develop around the resection cavity borders leading to patient death. We hypothesize that the local delivery of Lauroyl-gemcitabine lipid nanocapsule based hydrogel (GemC₁₂-LNC) in the tumor resection cavity of GBM is a promising strategy as it would allow to bypass the blood brain barrier, thus reaching high local concentrations of the drug. The cytotoxicity and internalization pathways of GemC₁₂-LNC were studied on different GBM cell lines (U251, T98-G, 9L-LacZ, U-87 MG). The GemC₁₂-LNC hydrogel was well tolerated when injected in mouse brain. In an orthotopic xenograft model, after intratumoral administration, GemC₁₂-LNC significantly increased mice survival compared to the controls. Moreover, its ability to delay tumor recurrences was demonstrated after perisurgical administration in the GBM resection cavity. In conclusion, we demonstrate that GemC₁₂-LNC hydrogel could be considered as a promising tool for the post-resection management of GBM, prior to the standard of care chemo-radiation.

胶质母细胞瘤（GBM）治疗包括在可能的情况下手术切除肿瘤，然后进行放射治疗和替莫唑胺口服化疗，但是在切除腔边界附近迅速发展复发，导致患者死亡。我们假设GBM肿瘤切除腔中基于月桂酰吉西他滨脂质纳米胶囊的水凝胶（GemC ₁₂ -LNC）的局部递送是一种有前途的策略，因为它可以绕过血脑屏障，从而达到较高的局部药物浓度。在不同的GBM细胞系（U251，T98-G，9L-LacZ，U-87 MG）上研究了GemC ₁₂ -LNC的细胞毒性和内在化途径。GemC ₁₂-LNC水凝胶在小鼠脑中注射时具有良好的耐受性。在原位异种移植模型中，肿瘤内给药后，与对照组相比，GemC ₁₂ -LNC显着提高了小鼠的存活率。此外，在GBM切除腔中进行围手术期给药后，证明了其延迟肿瘤复发的能力。总之，我们证明了GemC ₁₂ -LNC水凝胶可以被视为有前途的GBM切除后管理的工具，在护理化学放疗标准之前。