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Int J Pharm. 2018 Sep 5;548(1):522-529. doi: 10.1016/j.ijpharm.2018.07.033. Epub 2018 Jul 17.

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

Author information

1
Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 1200 Brussels, Belgium.
2
Université catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Avenue Mounier, 1200 Brussels, Belgium.
3
Université catholique de Louvain, Institute of Neurosciences, Avenue Mounier, 1200 Brussels, Belgium; Department of Neurosurgery, CHU UCL Namur, Avenue G. Thérasse 1, 5530 Yvoir, Belgium.
4
Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.

Abstract

Glioblastoma 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 into the resection cavity of GBM orthotopic model lead to more than 50% long-term survival mice (150 days) compared to the control groups (mean survival time 52 days). This significant delay of recurrence is very promising for the post-resection treatment of GBM.

KEYWORDS:

Glioblastoma; Hydrogel; Local delivery; Orthotopic model; PLGA nanoparticles; Paclitaxel

PMID:
30017818
DOI:
10.1016/j.ijpharm.2018.07.033
[Indexed for MEDLINE]

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