EVALUATION OF CHITOSAN NANOPARTICLES FOR DELIVERY OF POTENTIALLY ACTIVE INTEGRINS INHIBITORS IN GLIOBLASTOMAS

Abstract

Glioblastomas multiform (GBMs) are more invasive tumors of the central nervous system, their invasiveness is related to the interaction with extracellular matrix glycoproteins such as fibronectin and vitronectin. These integrins interact with glycoproteins present in tumor cells facilitating adhesion and migration of these cells into brain tissue. Integrins, ±5²1, ±v²5, and ±v²3 are strongly expressed in GBMs, and can be used as target molecules in cancer therapy in the central nervous system (CNS). Inhibitors of integrins known as disintegrins, have been considered potent inhibitors of cell adhesion and used to combat various diseases, including cancer. The cilengitide disintegrin have been studied against GBMs because it inhibits the ±V²3 integrin, ±5²1 and ±V²5. Another is the DisBa-01 disintegrin which specifically interacts with ±5²1 integrin ±V²3 and have exhibiting potent anti-tumor properties. However, the use of therapeutic proteins is often limited by the low stability in physiological fluids, immunogenic and allergenic potential, and the low bioavailability. To overcome these problems, have been developed new drug delivery systems and alternative routes of administration, for example, the nasal route. The nasal route have generated great interest as an alternative route for administration of proteins and the mucoadhesive systems have been employed to decrease the clearance of the formulation by the mucociliary clearance mechanisms, allowing greater contact between the formulation and site of absorption in the nasal cavity, besides to promoting passage of drugs through the blood brain barrier. Thus, this study aims to evaluate chitosan nanoparticles to act as carriers of disintegrins to the brain and promote the release in tumor site by inhibition of specific integrins present in glioblastomas and can be an alternative to anti-tumor therapy.