Post-resection treatment of glioblastoma with an injectable nanomedicine-loaded photopolymerizable hydrogel induces long-term survival

Publication date: 5 September 2018Source: International Journal of Pharmaceutics, Volume 548, Issue 1Author(s): Mengnan Zhao, Fabienne Danhier, Chiara Bastiancich, Nicolas Joudiou, Lakshmi Pallavi Ganipineni, Nikolaos Tsakiris, Bernard Gallez, Anne des Rieux, Aleksandar Jankovski, John Bianco, Véronique PréatAbstractGlioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite available therapeutic options, the prognosis for patients with GBM remains very poor. We hypothesized that the intra-operative injection of a photopolymerizable hydrogel into the tumor resection cavity could sustain the release of the anti-cancer drug paclitaxel (PTX) encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles and prevent GBM recurrence. The tumor was resected 13 days after implantation and a pre-gel solution composed of polyethylene glycol dimethacrylate (PEG-DMA) polymer, a photoinitiator and PTX-loaded PLGA nanoparticles (PTX PLGA-NPs) was injected into the tumor resection cavity. A solid gel filling the whole cavity was formed immediately by photopolymerization using a 400 nm light. PTX in vitro release study showed a burst release (11%) in the first 8 h and a sustained release of 29% over a week. In vitro, U87 MG cells were sensitive to PTX PLGA-NPs with IC50 level of approximately 0.010 μg/mL. The hydrogel was well-tolerated when implanted in the brain of healthy mice for 2 and 4 months. Administration of PTX PLGA-NPs-loaded hydrogel ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research