Nano-Biointerface studies of mucus-modulating particles containing Remdesivir with respiratory epithelium membrane models in healthy and hyperinflammatory conditions of COVID-19

• Grant number: 20/14062-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2021
• End date: April 30, 2023
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Valtencir Zucolotto
• Grantee: Leonardo Miziara Barboza Ferreira
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

The most serious cases of COVID-19 are manifested by a state of pulmonary hyperinflammation caused by a cytokine storm, which occurs due to the infection of the lower airways by the SARS-CoV-2 virus. Under these conditions, diffuse alveolar damage leads to severe acute respiratory disease (SARS), with a high mortality rate. Mucus-modulating nanoparticles are potentially useful in the pulmonary administration of drugs and vaccines for the treatment of COVID-19, as they could be designed to overcome the mucus barrier present in the airways and reach the alveolar region, which is covered by the lung surfactant barrier. Thus, the therapeutic and / or preventive success of these carriers depends on interactions occurring at the nano-bio interface of these two barriers present in the pulmonary administration route. The objective of this project is to characterize the nano-biointeractions of mucus-modulating particles containing the model drug remdesivir with real and biomimetic membranes of the respiratory epithelium. The studies will be performed with cells able to producing mucus and lung surfactant. These biointerfaces are relevant to SARS-CoV-2 infection and represent important sites for the release of remdesivir. The characterization of the biophysical properties of biological membranes (extracted from epithelial cells) and biomimetics (produced with synthetic lipids) will be performed using Langmuir films and phospholipid vesicles in the presence of particles in healthy and inflammatory conditions. The project conclusion will allow us to gain mechanistic insights into the main interactions occurring in these nano-biointerfaces that can fundamentally improve the rational design of mucus-modulating particles for pulmonary administration of drugs and vaccines for the treatment of COVID-19 and other serious respiratory syndromes. (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)

FERREIRA, LEONARDO M. B.; CARDOSO, VALERIA M. O.; PEDRIZ, IGOR DOS SANTOS; SOUZA, MAURICIO P. C.; FERREIRA, NATALIA N.; CHORILLI, MARLUS; GREMIAO, MARIA P. D.; ZUCOLOTTO, VALTENCIR. Understanding mucus modulation behavior of chitosan oligomers and dextran sulfate combining light scattering and calorimetric observations. Carbohydrate Polymers, v. 306, p. 14-pg., 2023-01-27. (20/14062-1)