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Multifunctional systems for the specific colonoscopy of bevacizumab for the treatment of Colorectal Cancer

Grant number: 19/10761-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2020
Effective date (End): June 30, 2023
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Maria Palmira Daflon Gremião
Grantee:Suzana Gonçalves Carvalho
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM

Abstract

Colorectal Cancer is a public health problem, among types of Cancer occupy the third position in terms of incidence and the second in mortality. For years, intravenous chemotherapy has been the therapeutic resource used in the treatment of Cancer, however, limited therapeutic efficacy and adverse effects compromise the use by this route. Bevacizumab (BVZ) was the first FDA approved (Food and Drug Administration) monoclonal Antibody (mAb) and has shown important advancement in antitumor therapy where survival overlaps toxicity. Due to the limitations of intravenous chemotherapy, antineoplastic therapy by non-parenteral routes, such as the oral route, represents the possibility of a home treatment, which offers a greater comfort and safety to the patient, which contributes significantly to the improvement of the quality of life of the patient and for adherence to the treatment. The development of site-specific drug delivery systems from the vectorization of the drug into the colon favors its selective pharmacological action at the tumor site and may improve therapeutic efficacy with reduced systemic toxicity. The association of strategies, such as the development of nanoparticles with mucoadhesive capacity and the incorporation of them in microparticles aiming at the protection of the system against the variable conditions of the gastrointestinal tract (GIT) represents a promising technological platform for specific colonization of BVZ. Bio/mucoadhesive properties of chitosan (QTZ) and Gellan Gum (GG) make them promising polymers in the development of mucoadhesive nanoparticles and natural polysaccharides resistant to enzymatic digestion in the upper segments of the TGI and with biodegradability dependent on colonic enzymes, such as Pectin (PEC) and Retrograded starch (RA) form a potential strategy for the development of microparticles. The present project aims to develop nanoparticles of GG and QTZ containing BVZ by the polyelectrolytic complexation method and incorporate them into microparticles based on AR and PEC. The systems will be characterized through analyzes of encapsulation efficiency, morphology, size, zeta potential, chemical, thermal, rheological and mucoadhesive properties. The performance of the system will be evaluated through in vitro release studies and evaluation of BVZ anti-angiogenic activity will be performed on Chorioallantoic Membrane (CAM) of chicken eggs (ex vivo). (AU)