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Evaluation of novel polymer nanoparticles as potential carriers for simultaneous release of a photosensitising agent and an active chemotherapeutic agent

Grant number: 19/04269-0
Support type:Regular Research Grants
Duration: August 01, 2019 - July 31, 2021
Field of knowledge:Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
Principal Investigator:Simone de Fátima Medeiros Sampaio
Grantee:Simone de Fátima Medeiros Sampaio
Home Institution: Escola de Engenharia de Lorena (EEL). Universidade de São Paulo (USP). Lorena , SP, Brazil
Assoc. researchers:Júlio César dos Santos ; Talita Martins Lacerda
Associated scholarship(s):19/18713-0 - Avaliação do potencial de novas nanopartículas poliméricas como agentes de encapsulação e liberação simultânea de um agente fotossensibilizador e um princípio ativo quimioterápico, BP.TT


Since most photosensitizing and chemotherapeutic agents are poorly soluble in water, leading to their rapid elimination from the bloodstream, encapsulation or association of such agents with suitable materials can improve their in vivo solubility and stability. Thus, this project aims to explore polymer nanoparticles, capable of combining photodynamic therapy (PDT) with chemotherapy in a single system for cancer therapy. The nanoparticles are based mainly on pullulan, a natural polymer produced from the fungus Aureobasidium pullulans and approved by the FDA for use in the pharmaceutical and cosmetic industry. Firstly, pullulan is partially grafted with poly(ethyleneglycol), since amphiphilic PEG-based materials can self-aggregate in aqueous medium, forming particles with furtive surface, reducing their recognition by the reticulo-endothelial system (RES) and, consequently, prolonging their circulation time in vivo. Poly(lysine) chains will also be grafted into pullulan via ring-opening polymerization, thereby obtaining the amphiphilic copolymers. Retinoic acid (vitamin A) will be incorporated into the polymers, in view its additional action as an inhibitor of cancer cells growth associated with its transition from a hydrophobic to hydrophilic state due to oxidation in the presence of singlet oxygen, which may cause destabilization of particles constituted by this molecule. Other molecules can be tested for the same purpose, depending on the evolution of the work. The next step will consist in preparing grafted pullulan nanoparticles through the micellar auto aggregation method, which will also be used to encapsulate an active substance used in cancer therapy fluorouracil (5-FU) and a photosensitizer, protoporphyrin IX (PPiX). The kinetics of chemotherapeutic agent in vitro release will be carefully evaluated in fluids that mimic the physiological environment. (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)
T. DE CARVALHO, LAYDE; DA S. PAULA, MARIA LUIZA; M. DE MORAES, RODOLFO; ALVES, GIZELDA M.; M. LACERDA, TALITA; DOS SANTOS, JULIO C.; M. DOS SANTOS, AMILTON; MEDEIROS, SIMONE DE F. Chemical Modification of Pullulan Exopolysaccharide by Grafting Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) via Click Chemistry. POLYMERS, v. 12, n. 11 NOV 2020. Web of Science Citations: 0.
CARVALHO, LAYDE T.; MORAES, RODOLFO M.; ALVES, GIZELDA M.; LACERDA, TALITA M.; SANTOS, JULIO C.; SANTOS, AMILTON M.; MEDEIROS, SIMONE F. Synthesis of amphiphilic pullulan-graft-poly(epsilon-caprolactone) via click chemistry. International Journal of Biological Macromolecules, v. 145, p. 701-711, FEB 15 2020. Web of Science Citations: 0.

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