Repurposing ebselen as an inhalable dry powder to treat respiratory tract infections

In this study, we developed inhalable ebselen dry powder formulations using a spray-drying technique. The amino acids leucine, methionine, and tryptophan were incorporated with ebselen to enhance the yield and aerosolization of the dry powders. The amino acid-containing ebselen dry powders showed a better yield (37-56.4 %) than the amino acid-free formulation (30.9 %). All dry powders were crystalline in nature. The mass median aerodynamic diameter (MMAD) was less than 5 µm for amino acids containing dry powders (3-4 µm) and slightly higher (5.4 µm) for amino acid free dry powder indicating their suitability for inhalation. The aerosol performance was higher when amino acids were used, and the leucine-containing ebselen dry powder showed the highest emitted dose (84 %) and fine particle fraction (68 %). All amino acid formulations had similar cytotoxicity as raw ebselen, tested in respiratory cell line (A549 cells), with half-maximal inhibitory concentrations (IC50) between 100 and 250 μg/mL. Raw ebselen and amino acid-containing dry powders showed similar potent antibacterial activity against the Gram-positive bacteria S. aureus and S. pneumoniae with minimum inhibitory concentrations of 0.31 μg/mL and 0.16 μg/mL, respectively. On the other hand, raw ebselen and the formulations showed limited antimicrobial activity against the Gram-negative pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae. In summary, in this study we were able to develop amino-acid-containi...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Source Type: research