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Injectable nanomedicine hydrogel for local chemotherapy of glioblastoma after surgical resection

2017; Elsevier BV; Volume: 264; Linguagem: Inglês

10.1016/j.jconrel.2017.08.019

1873-4995

Chiara Bastiancich, John Bianco, Kévin Vanvarenberg, Bernard Učakar, Nicolas Joudiou, Bernard Gallez, Guillaume Bastiat, Frédéric Lagarce, Véronique Préat, Fabienne Danhier,

Nanoparticle-Based Drug Delivery

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 (GemC 12 -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 GemC 12 -LNC were studied on different GBM cell lines (U251, T98-G, 9L-LacZ, U-87 MG). The GemC 12 -LNC hydrogel was well tolerated when injected in mouse brain. In an orthotopic xenograft model, after intratumoral administration , GemC 12 -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 GemC 12 -LNC hydrogel could be considered as a promising tool for the post-resection management of GBM, prior to the standard of care chemo-radiation.