Evaluation of synergic effect between CHC and cetuximab against glioblastoma using drug delivery systems

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 prognosis. The existence of physiological barriers, especially blood brain barrier (BBB), represents the main obstacle that limits adequate concentrations of the drugs designed to therapy. Due to their anatomical advantages, a strategy proposed for appropriate delivery to SNC involves the use of the nasal route of administration once it avoids the passage through the BBB, allowing sufficient drug concentrations to reach the brain by perineural channels. Little changes and survival improvements with resection thresholds have been reported through the use of associated therapies for cancer treatment. A multiple target approach might provide simultaneous interference on different signaling pathways, minimizing the occurrence of resistance. Although a series of therapy protocols using combined drugs have been tested, association aiming to inhibit epidermal grow factor receptor together with monocarboxylate transporters have not yet been attempted. We hypothesized that two already studied drugs (±-cyano-4-hydroxycinnamic acid and cetuximab) could synergize against GBM. Therefore, we proposed a new "double combination" therapeutic strategy against GBM, a possibility given by the development of polymeric drug delivery systems to be administered by the nasal route. Nanotechnology integrates this research giving technological tools that can provide selective drug delivery, facilitating drug internalization and promoting drug controlled release to the intracellular target.