Evaluation of the potential of intranasal administration of nanoparticles loaded with an anticancer protein for treatment of brain tumor

Abstract

Glioblastoma (GBM), the most malignant primary brain tumors, are characterized by highly aggressive and invasive growth throughout the brain that can be contributed to activating multiple oncogenic pathways including vascular endothelial growth factor (VEGF) signaling. The VEGF is the main factor involved in the pathological angiogenesis of GBM. The targeted therapy with the monoclonal antibody bevacizumab (BVZ) is a promising strategy to block VEGF signaling pathway. Despite of beneficial effect of BVZ, however, systemic delivery of monoclonal antibody to brain tumors remains a major problem, mainly due to difficulty penetrating the blood brain barrier (BBB). Furthermore, like other protein drugs, antibody formulations represent a great challenge due to its inherent physochemical instability in formulations and in biological fluids. To overcome these problems, we will integrate intranasal drug delivery (IND), noninvasive method of bypassing the BBB, with nanotechnology-based delivery systems. During the research stage at University of California San Francisco, BVZ loaded in nanoparticles will be evaluated in vitro in different GBM cell lines and in vivo in intracranial GBM xenograft model. (AU)