Maeva and Noé presented their poster at the SFNano C'Nano conference entitled "Preclinical evaluation of a paclitaxel nanoprodrug for glioblastoma therapy".
Glioblastoma (GBM) is a malignant central nervous system tumor with a median survival of 15 months despite standard treatment protocols combining surgery, chemotherapy and radiotherapy. Although it is active on GBM cells in vitro, paclitaxel (PTX) is not used against brain tumors because of its limited cerebral availability. Moreover, aqueous solubilization of PTX requires the use of excipients such as Cremophor EL®, occasionally causing serious allergic reactions.These hurdles may be overcome by a PTX nanoprodrug obtained by covalent grafting of PTX on water-soluble nanoparticles. Our results show these nanoparticles are safe and internalized in different cell lines, making them interesting drug carriers for hydrophobic drugs. The anticancer activity of nanoparticles-PTX conjugates was confirmed in vitro on GBM cell lines, albeit at several hundred-fold higher concentrations than free PTX. In vivo, paclitaxel nanoprodrug did not show anticancer activity in murine models at usual equivalent PTX doses (1 mg/kg, intratumoral administration) due to slow drug release not affording sufficiently high intratumoral PTX concentrations. However, these nanoparticles may be useful as a sustained-release form if used at higher doses. Moreover, these PTX nanoprodrugs are water-soluble, thus avoiding the use of potentially harmful excipients, and afforded concentrations equivalent to at least 1 g/L of PTX in saline, when the free PTX molecule would have been virtually insoluble.
