Evaluation of the potential of bevacizumab-functionalized liposomes or hyaluronic acid for incorporation of abiraterone in the treatment of prostate cancer

• Grant number: 18/23430-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): June 01, 2019
• Effective date (End): July 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal researcher: Maria Palmira Daflon Gremião
• Grantee: Kaio Pini Santos
• 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

Prostate cancer is the most incident neoplasm in men in the world. This neoplasm affects approximately 32% of the male population. Among the chemotherapeutics recently employed in therapy, we highlight the abiraterone, which acts in inhibition of the enzyme CYP17 (responsible for the synthesis of androgens). Abiraterone was approved by the Food and Drug Administration (FDA) in 2012 for use in the treatment of prostate cancer. It is indicated mainly for prostatic neoplasias resistant to castration; presenting an efficiency in the regression of the tumor in 65% of the cases. However, this drug has reduced selectivity to cancer cells and, like the vast majority of chemotherapeutics, is responsible for a wide range of unwanted side effects due to its interaction with healthy cells. A promising strategy in order to potentiate the selectivity of this drug and decrease its side effects is the incorporation into functionalized liposomes. Among the innumerable possibilities of functionalization, this work focuses on two different functionalizers: bevacizumab, which is a monoclonal antibody with high specificity for vascular endothelial growth factor (VEGF). This specificity aims to decrease the formation of new vessels, consequently reducing the vascularization in the tumor tissue. And the second vectorization tested will be using hyaluronic acid, a natural ligand of the CD44 receptor and overexpressed in several types of cancer, among them, prostate cancer. Overexpression of this receptor is increased with cancer progression. The vectorization of liposomes, both by bevacizumab and hyaluronic acid, proves to be an interesting option to potentiate selectivity in the delivery of abiraterone associated with the advantages of drug loading by a nanostructured system. In the light of the above, the objective of this work is to develop liposomes for abiraterone transport with two different types of independent functionalization and to evaluate its potential in the treatment of prostate cancer. The physicochemical characterization will be done with the use of several techniques. The uptake (endocytosis) and location of the liposomes in the cellular environment will be evaluated by confocal microscopy. Finally, liposomes will be evaluated for efficacy in prostate cancer therapy by in vitro cytotoxicity studies in neoplastic cell lines.

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)

DI FILIPPO, LEONARDO DELELLO; DOS SANTOS, KAREN CRISTINA; HANCK-SILVA, GILMAR; DE LIMA, FELIPE TITA; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. A Critical Review of Biological Properties, Delivery Systems and Analytical/Bioanalytical Methods for Determination of Bevacizumab. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, v. 51, n. 5, p. 445-453, JUL 4 2021. Web of Science Citations: 3.

DOS SANTOS, KAREN CRISTINA; DOS REIS, LEIDIANA ROCHA; RODERO, CAMILA FERNANDA; SABIO, RAFAEL MIGUEL; JUNIOR, ALBERTO GOMES TAVARES; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, NOV 2020. Web of Science Citations: 0.