Preclinical evaluation of N-acetyl-cysteine in association with liposomes of lung surfactant's lipids for the treatment of pulmonary fibrosis and asthma

MORALES, ESTEFANÍA N.; MALECKI, CONSTANZA CONFINO; MARURI, ALEJANDRO; SÁNCHEZ, VANESA R.; PORTU, AGUSTINA; GOLDMAN, ALEJANDRA; CHIARAMONI, NADIA S.; FENOY, IGNACIO M.

TOXICOLOGY AND APPLIED PHARMACOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2025 vol. 502

0041-008X

Purpose: There is a need to generate new treatments against pulmonary diseases such as idiopathic fibrosis and asthma. N-acetylcysteine (NAC) has multiple clinical applications, but its unstable nature and route of administration limits its effectiveness. New pulmonary delivery strategies, such as liposomes made of lung surfactant lipids, could overcome NAC’s limitations. This work aims to evaluate the efficacy of NAC combined with liposomes as a treatment for asthma and in preventing fibrotic development. Methods: Unilamellar vesicles were obtained through the dehydration-rehydration method followed by multiple membrane extrusion and characterized by Dynamic Light Scattering and Transmission electron microscopy. Lung f ibrosis was induced by bleomycin administration, and liposomal formulation of NAC (LipoNAC) was evaluated as a preventive treatment. LipoNAC formulation was also evaluated in a therapeutic regimen for asthma using the classic ovalbumin model. For both models, the administration of the treatment was via the intranasal route. Results: NAC treatments (free NAC and LipoNAC) improved lung histopathology and decreased collagen deposition when tested in the lung fibrosis model. Only LipoNAC decreased serum levels of lactate dehydrogenase, myeloperoxidase activity in lung fluid and lung TGF-β. Although both treatments decreased Th2 cytokine and histopathological inflammation in the asthma model, only LipoNAC treatment significantly decreased mucus in asthmatic mice. Conclusions: These results indicate that surfactant liposomal delivery of NAC potentiates its anti-inflammatory, mucolytic, and antioxidant activity, rendering it a promising therapy for respiratory diseases.