Inhaled ibuprofen-duo treatment: security, kinetic, and effects

VOLPINI XIMENA; NATALI LAUTARO; TEJERINA DAVID; FARFAN SILVIA; AMIGONE JOSÉ LUIS; MOYA MARTÍN; MUSRI MELINA

Congreso; LXX Reunión anual de la Sociedad Argentina de Inmunología (SAI). 16-19 de noviembre. Mar del Plata. Buenos Aires Argentina; 2022

Water-soluble Ibuprofen constitutes a critical strategy for inhalation-based treatments of respiratory diseases. Sodium ibuprofenateamphipathic Luarprofen is an inhalable formulation with high lungbioavailability with the ability to inhibit the enzyme Cyclooxygenase,decrease reactive oxygen species concentration, and reduce localairway inflammation in patients. Here, we aim to evaluate the kinetics, security, and effects of Luarprofen duo (LD, Química Luar®) formulation in murine models. To this end, we designed administrationboxes connected to a nebulizer with a gas exchange compressor.Adult B6 mice of both sexes were nebulized with the vehicle, LD 1X,or LD 1.5X for 20 min. To evaluate the kinetic and pharmaco-security, the procedure was performed 3 times/day for 14 days. Blood and lung concentration of LD, blood gas profile, biomarkers of liverand kidney damage, and lung histology were analyzed immediatelyafter 14 days of daily treatment, and after 14 days of the end of thetreatment (resting). We did not find any differences between sexes. High-pressure liquid chromatography showed high LD concentrations immediately in blood after nebulization and progressivelydecreased until values statistically undistinguishable from controlsafter 2 h. The drug was also distributed in the lungs, reaching maximum values 2 h after nebulization. LD 1X or 1,5X did not affect theprofiles of hemoglobin, arterial gases, and blood acid-base. Also,LD did not cause liver damage, altered kidney function, or increasedacute phase protein levels. Importantly, vascular, alveolar, and/orbronchial histological changes were not observed in the lungs. Finally, we evaluated the effects of LD 1X in a model of LPS-inducedacute pulmonary inflammation. The drug attenuated the excessivepulmonary infiltration of inflammatory cells and improved the gasexchange. LD would be a novel, safe, and promising therapeuticstrategy for inflammatory-lung diseases.