Ciprofloxacin nanocrystals and N-acetylcysteine co-solidified powders for pulmonary drug delivery: development and in vitro and in vivo characterization

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 24; no. 2
• Main Authors: Guan, Wenhao, Liu, Yanchao, Ding, Shuaijie, Wang, Yancai
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2022; Springer Nature B.V
• Subjects: Acetylcysteine; Aerosols; Antibiotics; Bioavailability; Characterization and Evaluation of Materials; Chemistry and Materials Science; Ciprofloxacin; Crystals; DNA damage; Drug delivery; Drug delivery systems; Feasibility studies; Fibers; Freeze drying; In vivo methods and tests; Inorganic Chemistry; Lactose; Lasers; Materials Science; Nanocrystals; Nanotechnology; Optical Devices; Optics; Particle size distribution; Permeability; Photonics; Physical Chemistry; Polyethylene glycol; Powder; Research Paper; Sputum; Stability analysis; Synergistic effect; Spray drying; DSPE-mPEG; Nanocrystals; Ciprofloxacin; Dry powder inhalations
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-022-05427-1

This study evaluated the feasibility of ciprofloxacin nanocrystals dry powder inhalations (DPIs) co-delivered with N-acetylcysteine (NAC) to improve the drug permeability and pulmonary bioavailability. The NAC could be reducing the viscosity of the sputum and causing it to liquefy, by breaks DNA fibers in sputum and purulent sputum. The ciprofloxacin nanocrystals, stabilized by 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine grafted N-[methoxy (polyethylene glycols)-2000] (DSPE-mPEG 2000 ), was prepared by anti-solvent precipitation technology. The powder contained ciprofloxacin nanocrystals and N-acetyl-cysteine was obtained as a result of freeze-drying and spray-drying, respectively. The powder was coupled with inhaled lactose and the DPI of ciprofloxacin nanocrystals/NAC co-delivery system was obtained. The in vitro characteristics, including particle size and distribution, morphology, crystalline state, stability, flowability, aerosol performance, and in vivo image were evaluated. The spray-dried DPI of ciprofloxacin nanocrystals/NAC co-delivery system exhibited stratified in vitro and in vivo aerosol performance. This study demonstrated that spray-dried DPI system with a synergistic effect and meanwhile a better flowability is desirable for enhanced pulmonary drug delivery without severe lung injury.