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Combinatorial therapy using polymersomes decorated with transferrin and incorporated into chitosan hydrogels as smart drug delivery systems for melanoma tumor cells

Grant number: 17/10789-1
Support type:Research Grants - Young Investigators Grants
Duration: June 01, 2018 - May 31, 2022
Field of knowledge:Engineering - Biomedical Engineering
Principal Investigator:André Moreni Lopes
Grantee:André Moreni Lopes
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas, SP, Brazil
Assoc. researchers:Carlota de Oliveira Rangel Yagui ; Leandro Ramos Souza Barbosa ; Luciana Biagini Lopes ; Priscila Gava Mazzola
Associated scholarship(s):18/10799-0 - Combinatorial therapy using polymersomes decorated with transferrin and incorporated into chitosan hydrogels as smart drug delivery systems for melanoma tumor cells, BP.JP

Abstract

In this research project, we propose to investigate a novel co-therapy approach using smart drug delivery systems in melanoma therapy. This approach will employ multi-drug delivery from nanostructures of polymer vesicle-type, otherwise known as polymersomes (Ps), which represents an innovative alternative for the treatment of cancer. Specifically, vemurafenib, a specific inhibitor of mutated B-Raf protein at the V600E site, and doxorubicin, a broad spectrum drug, that can act on wild B-Raf proteins (non-mutated), correspond in two important drugs for melanoma cancer therapy. Co-encapsulation of these drugs in Ps can favor not only the stability of the molecules, but also increase the half-life of these molecules in the bloodstream and also possible synergistic effect for tumor cells. In addition to this approach, we propose the use of three-dimensional (3-D) structures of chitosan hydrogels as platforms of Ps. We expect this platform to have advantages such as mucoadhesiveness, biocompatibility and controlled and sustained release, which makes it potentially interesting for application in transdermal route for drug delivery. Moreover, by decorating the surface of these nanostructures with affinity ligand such as transferrin (Tf), we can increase the specificity of Ps toward tumor cells and achieve a greater therapeutic efficacy and decrease of toxicity. In this work, it will be investigated: (i) development of Ps in different conditions, (ii) drug encapsulation (individual and simultaneous), (iii) decoration of Ps with Tf, (iv) characterization of Ps formulations, (v) stability and incorporation of Ps in the chitosan hydrogels under different conditions, (vi) stability of the hydrogel with and without Ps, (vii) Ps release incorporated into the hydrogel in conditions simulating the transdermal route, and (viii) comparison of cytotoxic effect in tumor cells (either BRAF mutated or not) versus normal cells. (AU)