Ms. Inbar Schlachet, Ph.D. Candidate
Department of Materials Science and Engineering,
Technion – Israel Institute of Technology Haifa 3200003, Israel
Central nervous system (CNS) tumors are a leading cause of childhood death due to cancer. Most of the tumors are diffuse intrinsic pontine gliomas (DIPG). This tumor fully conserved by the blood-brain barrier (BBB), the anatomical barrier that protects the CNS and prevents drugs penetration. Based on recent progress in the disease biology, two candidate drugs that inhibit two pathways upregulated in DIPG were examined. The direct nose-to-brain pathway that bypasses the BBB is very promising to target nanoencapsulated drugs to the CNS. Polymeric micelles (PMs) emerged as potential nanotechnology for drug delivery to the CNS intranasally (i.n.). In this work, we investigated and characterized mixed mucoadhesive amphiphilic nanoparticles (NPs) made of chitosan and poly(vinyl alcohol) that were hydrophobized with poly(methyl methacrylate) blocks and used them to produce self-assembled NPs for the drugs encapsulation. The compatibility and uptake of the NPs was evaluated in vitro in patient-derived DIPG cells and nasal epithelium cells model. Next, the NPs permeability was evaluated in a nasal epithelium cell monolayer. Results indicated that the mixed mucoadhesive NPs display good drug loading capacity, and up-taken by DIPG cells. In addition, the NPs cross the nasal epithelium in vitro mainly by paracellular pathway. Moreover, we assessed the anti-cancer activity by determined the inhibitory concentration 50 of both drugs in DIPG cells. The drugs display high anti-DIPG efficacy in vitro. Finally, the biodistribution of the NPs after i.n. and intravenous was evaluated in mice.