New aerosol formulation to control ciprofloxacin pulmonary concentration - Archive ouverte HAL Access content directly
Journal Articles Journal of Controlled Release Year : 2017

New aerosol formulation to control ciprofloxacin pulmonary concentration

(1) , (2) , (1) , (3) , (1, 3) , (2) , (1) , (1)


Ciprofloxacin (CIP) apparent permeability across a pulmonary epithelium model can be controlled by the affinity of its complex with a metal cation. The higher the complex affinity, the larger is the reduction in CIP apparent permeability. The aim of this study was to evaluate if the control of the CIP apparent permeability observed in vitro could be transposed in vivo to control the CIP lung-to-blood absorption rate and CIP concentrations in the lung epithelial lining fluid (ELF) after intratracheal (IT) administration. Two types of innovative inhalable mi-croparticles loaded with the low-affinity CIP-calcium complex (CIP-Ca) or with the high-affinity CIP-copper complex (CIP-Cu) were formulated and characterized. Then, ELF and plasma pharmacokinetics of CIP were studied in rats after IT administration of these two types of microparticles and of a CIP solution (2.5 mg/kg). The presence of Cu 2 + had little effect on the microparticle properties and the dry powder had aerodynamic properties which allowed it to reach the lungs. CIP concentrations in ELF were much higher after CIP-Cu micro-particles IT administration compared to the other two formulations, with mean AUC ELF to AUC u,plasma ratios equal to 1069, 203 and 9.8 after CIP-Cu microparticles, CIP-Ca microparticles and CIP solution pulmonary administration, respectively. No significant modification of lung toxicity markers was found (lactate dehy-drogenase and total protein). CIP complexation with Cu 2 + seems to be an interesting approach to obtain high CIP concentrations in the ELF of lungs after dry powder IT administration.
Embargoed file
Embargoed file
Ne sera jamais visible

Dates and versions

inserm-02379277 , version 1 (25-11-2019)



Barbara Lamy, Dolores Remedios Serrano, Isabelle Lamarche, Patrice Gobin, William Couet, et al.. New aerosol formulation to control ciprofloxacin pulmonary concentration. Journal of Controlled Release, 2017, 271, pp.118-126. ⟨10.1016/j.jconrel.2017.12.021⟩. ⟨inserm-02379277⟩
80 View
1 Download



Gmail Facebook Twitter LinkedIn More