Nanostructured multifunctional systems for drug controlled release through nasal route on glioblastomas treatment

Abstract

Glioblastomas (GBM) account 77% of malignant tumors that occurs on central nervous system (SNC) and today, despite all advances in chemotherapy, radiotherapy and neurosurgery, remains with limited prognoses. The existence of physiological barriers, especially blood brain barrier (BBB), represents the main obstacle that limits appropriate concentrations of the drugs designed to GBM therapy. Due their anatomical advantages, a strategy propose for appropriate delivery of therapeutic agents to SNC involves the use of nasal route of administration once it avoids the passage through the BBB, allowing appropriated drug concentrations reach the brain by perineural channels. In parallel, the understanding about molecular features of tumor cells combined with biophysics, chemistry and pharmacology research suggests that therapy of cancer pathology should include multiple target approach, which provides simultaneous interference on different signaling pathways, minimizing the occurrence of resistance. Nanotechnology integrates these research giving technological tools that might provide selective drug delivery, facilitate drug internalization and promote therapeutic agent controlled release against the intracellular target. Fallowing this rationality, this research project proposes rational design of multifunctional nanoparticles combining the use of alginate and chitosan polymers due their mucoadhesive properties and ability to interact with mucus constituents; a combination of cetuximab drug, monoclonal antibody against epidermal growth factor receptor which inhibit the production of pro-angiogenic factors and alpha-cyano-4-hydroxycinnamic acid (CHC), wich prevent monocarboxylate transporters (MCTs) activity responsible for lactate efflux to extracellular medium, promoting tumor cells death by acidosis and advantages offered by nasal route to reach SNC, allowing a new and favorable future on GBM treatment. (AU)