Leucine enhances aerosol performance of Naringin dry powder and its activity on cystic fibrosis airway epithelial cells

The effect of different amino acids (AAs) on the aerosol performance of N spray-dried powders was studied. Morphology, size distribution, density, dissolution rate were evaluated and correlated to process parameters. The aerosol performance was analyzed by both Single Stage Glass Impinger and Andersen Cascade Impactor. Results indicated that powders containing 5% (w/w) of leucine, proline or histidine and dried from 3:7 ethanol/water feeds showed very satisfying aerodynamic properties with fine particle fraction > 60%. Both neat N (raw and spray-dried) and N-leu1 dry-powder showing good aerodynamic properties were tested in cystic fibrosis (CF) and normal bronchial epithelial cells. Cell proliferation and expression levels of the key enzymes of the NF-κB and MAPK/ERK pathways, overactivated in CF cell lines, were evaluated. N-leu1 was able to significantly inhibit the expression levels of IKKα, IKKβ, as well as of the direct NF-κB inhibitor, IκBα. In addition N-Leu1 inhibited phosphorylation of ERK1/2 kinase and did not reduce cell proliferation as observed for the neat raw drug. Leucine co-spray-dried with the drug improved both aerodynamic properties and in vitro pharmacological activity of Naringin. The optimized N-Leu formulation as dry powder is potentially able to reduce hyperinflammatory status associated to CF.

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