New aerosol formulation to control ciprofloxacin pulmonary concentration

Abstract : 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.
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Submitted on : Monday, November 25, 2019 - 3:53:54 PM
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Barbara Lamy, Frédéric Tewes, Dolores Serrano, Isabelle Lamarche, Patrice Gobin, et al.. New aerosol formulation to control ciprofloxacin pulmonary concentration. Journal of Controlled Release, Elsevier, 2017, 271, pp.118-126. ⟨10.1016/j.jconrel.2017.12.021⟩. ⟨inserm-02379277⟩

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