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

• Grant number: 19/10761-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2020
• Effective date (End): December 31, 2023
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Palmira Daflon Gremião
• Grantee: Suzana Gonçalves Carvalho
• Host 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
• Associated scholarship(s): 21/08699-0 - In vitro evaluation of biocompatibility, intestinal permeability, and anticancer properties of multifunctional systems intended for colonic release of bevacizumab in the treatment of colorectal cancer, BE.EP.DR

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CARVALHO, SUZANA GONCALVES; POLLI SILVESTRE, AMANDA LETICIA; DOS SANTOS, ALINE MARTINS; FONSECA-SANTOS, BRUNO; RODRIGUES, WINNER DUQUE; DAFLON GREMIAO, MARIA PALMIRA; CHORILLI, MARLUS; OLIVEIRA VILLANOVA, JANAINA CECILIA. olymeric-based drug delivery systems for veterinary use: State of the ar. International Journal of Pharmaceutics, v. 604, JUL 15 2021. (19/10761-5)

DOS SANTOS, ALINE MARTINS; CARVALHO, SUZANA GONSALVES; MENEGUIN, ANDREIA BAGLIOTTI; SABIO, RAFAEL MIGUEL; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. Oral delivery of micro/nanoparticulate systems based on natural polysaccharides for intestinal diseases therapy: Challenges, advances and future perspectives. JOURNAL OF CONTROLLED RELEASE, v. 334, p. 353-366, JUN 10 2021. (19/10761-5)