The rough inhalable ciprofloxacin hydrochloride microparticles based on silk fibroin for non-cystic fibrosis bronchiectasis therapy with good biocompatibility.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease, and the thick and viscous mucus covering on respiratory epithelia can entrap the inhaled drugs, resulting in compromised therapeutic efficiency. In order to solve this problem, the inhalable ciprofloxacin hydrochloride microparticles (CMs) based on silk fibroin (SF) and mannitol (MAN) were designed and developed. SF was applied to increase the loading efficiency of ciprofloxacin hydrochloride by strong electrostatic interactions. MAN could facilitate the penetration of drugs through mucus, which ensured the drugs could reach their targets before clearance. Furthermore, the aerodynamic performance of the inhalable microparticles could be tuned by changing the surface roughness to achieve a high fine particle fraction value (45.04%). The antibacterial effects of CMs were also confirmed by measuring the minimum inhibitory concentration against four different bacteria strains. Moreover, a series of experiments both in vitro and in vivo showed that CMs would not affect the lung function and induce the secretion of inflammatory cytokines in lungs, demonstrating their excellent biocompatibility and biosafety. Therefore, CMs might be a promising pulmonary drug delivery system for the treatment of NCFB.