Ph responsive hydrogels as potential drug delivery system for bevacizumab administration

• Grant number: 13/21824-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2014
• End date: November 30, 2015
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Palmira Daflon Gremião
• Grantee: Natália Noronha Ferreira Naddeo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 15/04734-4 - Evaluation of tumor growth and antiangiogenic activity of pH responsive drug delivery systems containing bevacizumab: in vivo studies, BE.EP.MS

Abstract

Cancer is a global problem responsible for approximately 13% of deaths worldwide. The process of angiogenesis plays an essential role in tumor growth, invasion and metastasis. Among the growth factors and cytokines related to this process, Vascular Endothelial Growth Factor (VEGF) is presented as a key aspect in pathological situations involving neovascularization such as cancer. Bevacizumab, a monoclonal antibody that will be used in this study, acts by inhibiting the process of angiogenesis which accompanies tumor tissue causing a reduction in tumor size. However, like other drugs of protein nature, antibody formulations represent a big challenge both from a technological and a biopharmaceutical standpoint. The low physical-chemical stability of proteins in biological fluids and formulations, as well as low bioavailability and immunogenic potential, requires searching for new strategies to circumvent these problems. "Smart" Hydrogels come as a promising alternative to overcome such problems, constituting systems capable of combining suitable release profile of the drug in physiological conditions of the body through its gelation ability promoted by stimuli such as pH change , very common in tumor regions . In this sense, the goal of this work is to develop pH-responsive alginate hydrogels as potential drug delivery systems for bevacizumab therapy in various cancers. The systems will be characterized by rheology, mechanical analysis, swelling profile, pH effect, incorporation capacity, release profile and in vitro antiangiogenic activity. (AU)