Preclinical Evaluation of N-Acetyl-Cysteine in Association with Liposomes of Lung Surfactant’s Lipids for the Treatment of Pulmonary Fibrosis and Asthma

ESTEFANÍA MORALES; A GOLDMAN; CHIARAMONI; FENOY, I

Congreso; Proceedings 2nd International Congress on nano and Biotechnology (ICNB2); 2023

RATIONALE: N-acetyl-cysteine (NAC) has potential as treatment of pulmonary diseases, but its low bioavailability limits its effectiveness. New pulmonary delivery strategies, such as liposomes made of lung surfactant lipids, could overcome NAC´s bioavailability limitations. This study aims to evaluate the effectiveness of NAC associated with liposomes in treating experimental lung fibrosis and asthma models.METHODS: Unilamellar vesicles were obtained by the dehydration-rehydration method followed by multiple membrane extrusion. The size was evaluated by DLS. Lung fibrosis was induced by bleomycin administration. A preventive treatment approach was performed with NAC or Liposomal NAC. A classic model of asthma against ovalbumin was used to evaluate treatment with NAC. RESULTS: Liposome size ranged from 200 nm and NAC reduced the size of the liposomes. In the lung fibrosis model, both NAC treatments (NAC and NAC-Lip) exerts lung histopathological change and decreased collagen deposition. Only NAC-Lip decreased serum levels of lactate dehydrogenase, myeloperoxidase activity in lung fluid and lung TGF-beta. Although both treatments decreased Th2 cytokine IL-5 and histopathological inflammation in the asthma model, only NAC-lip treatment significantly decreased mucus against asthmatic mice. CONCLUSIONS:The liposomal delivery of NAC potentiates its anti-inflammatory, mucolytic, and antioxidant activity, making it a promising therapy for respiratory diseases.