Journal
JOURNAL OF CONTROLLED RELEASE
Volume 271, Issue -, Pages 118-126Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.12.021
Keywords
Ciprofloxacin; Dry powder; Aerosol; Controlled permeability; Pharmacokinetics; Pulmonary delivery
Funding
- Irish Research Council and Campus France under the Ulysses Scheme [320032B]
- Science Foundation Ireland [SFI/12/RC/2275]
- University Hospital of Poitiers, France
Ask authors/readers for more resources
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 microparticles 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 Cu2+ 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 microparticles 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 dehydrogenase and total protein). CIP complexation with Cu2+ seems to be an interesting approach to obtain high CIP concentrations in the ELF of lungs after dry powder IT administration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available