Journal
JOURNAL OF CONTROLLED RELEASE
Volume 225, Issue -, Pages 283-293Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.01.054
Keywords
Lipid nanocapsules; Gemcitabine; Hydrogel; Nanomedicine; Glioblastoma
Funding
- Education, Audiovisual and Culture Executive Agency (EACEA) of the European Commission of the Erasmus Mundus Joint Programme NanoFar
- Universite catholique de Louvain (F.S.R.)
- Fonds National de la Recherche Scientifique (F.R.S. - FNRS)
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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 (GemC(12)-LNC) in order to obtain a sustained and local delivery of this drug in the brain. In this study, the GemC(12)-LNC has been formulated and characterized and the viscoelastic properties of the hydrogel were evaluated after extrusion from 30 G needles. This system showed a sustained and prolonged in vitro release of the drug over one month. GemC(12) and the GemC(12)-LNC have shown increased in vitro cytotoxic activity on U-87 MG glioma cells compared to the parent hydrophilic drug. The GemC(12)-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 GemC(12)-LNC hydrogel for the local treatment of GBM. (C) 2016 Elsevier B.V. All rights reserved.
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