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Multifunctional molecule delivery to treat pulmonary infections and consequent local inflammation


Community-acquired pneumonia (CAP) has the highest mortality among current infections. Despite being predominantly bacterial, one third of the global cases of CAP had a viral etiology, referring to approximately 100 million cases (2016). In 2019-2020, the respiratory virus Sars-Cov-2 alone caused 280 thousand deaths in 215 countries (until 12/05/2020, the vast majority with cases of pneumonia). However, severe viral pneumonia requires hospitalization and exposes the patient to the risk of co-infection by bacteria, which requires antibiotics on hospital admission. The severity of pneumonia is often related to a deleterious inflammatory profile of the lung, resulting from an exacerbated reaction of the immune system and / or ischemia (coronavirus). Therefore, anti-inflammatory drugs are often administered, in addition to anticoagulants (if necessary). If patients have comorbidities, they should continue with their previous medications, increasing the risk of drug interactions. In these situations, the use of multifunctional molecules can decrease the number of drugs required and simplify pharmacotherapy. Modification of the route of administration also benefits the treatment: pulmonary disease can provide high local drug concentration and decrease systemic exposure, the incidence of side effects and / or risks of drug interaction. However, highly permeable drugs can quickly enter the circulation, requiring formulation that promotes local residence. Given the above, this project focuses on the development of nanostructured formulations of antibiotics and antiviral potentials, with anti-inflammatory action, for pulmonary administration via inhalation. The formulations will be characterized and selected according to their physicochemical, antiviral (Sars-Cov-2), antibacterial (strains that infect the respiratory tract), cytotoxic, anti-inflammatory and permeability properties in pulmonary cell layer in vitro. Effective in vitro formulations will be tested on animal models in a complementary project. Finally, we have only one inhaled antibiotic produced in Brazil (tobramicin, not used for PAC) and few related researches, highlighting the technological relevance of the project at the national level. (AU)

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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)
FEITOSA, RENATA CARVALHO; AKIOKA ISHIKAWA, ELINA SAWA; ALVES DA SILVA, MARIANA FARIAS; DA SILVA-JUNIOR, ARNOBIO ANTONIO; OLIVEIRA-NASCIMENTO, LAURA. Five decades of doxycycline: Does nanotechnology improve its properties?. International Journal of Pharmaceutics, v. 618, p. 16-pg., . (20/08059-8, 19/08281-5)
BERALDO-ARAUJO, VIVIANE LUCIA; SIQUEIRA VICENTE, ANA FLAVIA; LIMA, MARCELO VAN VLIET; UMERSKA, ANITA; SOUTO, ELIANA B.; TAJBER, LIDIA; OLIVEIRA-NASCIMENTO, LAURA. Levofloxacin in nanostructured lipid carriers: Preformulation and critical process parameters for a highly incorporated formulation. International Journal of Pharmaceutics, v. 626, p. 13-pg., . (20/08059-8, 19/09719-4, 18/03666-3)
CARVALHO FEITOSA, RENATA; SOUZA RIBEIRO COSTA, JULIANA; VAN VLIET LIMA, MARCELO; SAWA AKIOKA ISHIKAWA, ELINA; COGO MULLER, KARINA; BONIN OKASAKI, FERNANDO; SABADINI, EDVALDO; GARNERO, CLAUDIA; LONGHI, MARCELA RAQUEL; LAVAYEN, VLADIMIR; et al. Supramolecular Arrangement of Doxycycline with Sulfobutylether-beta-Cyclodextrin: Impact on Nanostructuration with Chitosan, Drug Degradation and Antimicrobial Potency. PHARMACEUTICS, v. 15, n. 4, p. 18-pg., . (19/08281-5, 20/08059-8)

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