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


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)

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Scientific publications (5)
(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, 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, . (19/04269-0)
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, . (19/04269-0)
MAIA, LANA S.; DE BOMFIM, ANNE SHAYENE C.; DE OLIVEIRA, DANIEL M.; PINHATI, FERNANDA R.; DA CONCEICAO, MONIQUE O. T.; BARUD, HERNANE S.; MEDEIROS, SIMONE A.; ROSA, DERVAL S.; MULINARI, DANIELLA R.. Tuning of renewable sponge-like polyurethane physical-chemical and morphological properties using the pullulan as a reactive filler. Journal of Applied Polymer Science, v. N/A, p. 13-pg., . (19/04269-0, 20/13703-3)
CARVALHO, LAYDE T.; VIEIRA, THIAGO A.; ZHAO, YANJUN; CELLI, ANNAMARIA; MEDEIROS, SIMONE F.; LACERDA, TALITA M.. Recent advances in the production of biomedical systems based on polyhydroxyalkanoates and exopolysaccharides. International Journal of Biological Macromolecules, v. 183, p. 1514-1539, . (19/04269-0, 19/12940-4)
SILVA, RODRIGO DUARTE; DE CARVALHO, LAYDE TEIXEIRA; DE MORAES, RODOLFO MINTO; MEDEIROS, SIMONE DE FATIMA; LACERDA, TALITA MARTINS. Biomimetic Biomaterials Based on Polysaccharides: Recent Progress and Future Perspectives. MACROMOLECULAR CHEMISTRY AND PHYSICS, v. N/A, p. 19-pg., . (19/04269-0, 19/12940-4, 20/11104-5)

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