Solid Lipid Nanoparticles Loaded with Antitumor Lipophilic Prodrugs Aimed to Glioblastoma Treatment: Preliminary Studies on Cultured Cells

The treatment of glioblastoma multiforme (GBM), the most malignant human glioma, is hampered mainly by the polyclonality and by the invasion modalities of the tumor, by the cell resistance to therapy and by the blood-brain barrier (BBB) presence. Solid lipid nanoparticles (SLN) have been recently proposed as vehicles for anticancer drugs for GBM treatment, according to their ability to enhance drug uptake by BBB endothelial cells and to evade cell resistance mechanisms. Moreover, their surface can be engineered in order to be selectively directed towards BBB. Nevertheless, many anticancer drugs are too hydrophilic to be loaded in the lipid matrix. In this experimental work an innovative formulation technology, named coacervation, was employed for SLN preparation, while anticancer drug loading was obtained through a lipophilic prodrug synthetic approach. Preliminary aims were the assessment of the cytotoxicity of the obtained formulations against GBM cultures obtained from human primary tumors, and of their potentiality in BBB overcoming by using cellular models. The encouraging results obtained with various anticancer drugs will pulse further studies in animal models in order to investigate their in vivo fate.