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

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 fibrosis 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.