Liposome Delivery of Ciprofloxacin Against Intracellular Francisella Tularensis Infection

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Authors
  1. Wong, J.P.
  2. Yan, H.
  3. Bissetti, K.L.
  4. Schnell, G.
  5. Conley, J.
  6. Schofield, L.N.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN)
Abstract
The effect of liposome delivery on the controlled release and therapeutic efficacy of ciprofloxacin against intracellular Francisella tularensis infection in vivo was evaluated in this study. Ciprofloxacin was encapsulated in small unilamellar vesicles by a remote loading procedure using an ammonium sulfate gradient. This procedure produced uniform sized liposomes (100 nm) with an entrapment rate of 90 + or – 3.5%. Following adminisatration of unencapsulated or liposome-encapsulated ciprofloxacin by intravenous injection of aerosol inhalation, levels of ciprofloxacin in sera, lungs, liver and spleen were determined using 14C-ciprofloxacin as radiotracer for ciprofloxacin. Intravenous injection of liposome-encapsulated ciprofloxacin resulted in higher serum levels of drug in serum, as well as increased drug retention in lungs, liver and spleen, compared to that of free encapsulated drug. Aerosol administration of liposome-encapsulated ciprofloxacin by jet nebulization resulted in significantly higher drug levels and prolonged drug retention in the lower respiratory tract compared to the free drug. Aerosol inhlation of liposome-encapsulated ciprofloxacin, given either prophylactically or therapeutically, provided complete protection in mice against a pulmonary lethal infection model of F. tularensis. In contrast, ciprofloxacin given in its free form, was ineffective. These results suggest that liposome encapulation of ciprofloxacin enhances drug delivery to the primary site o
Keywords
Ciprofloxacin;Drug delivery;Inhalation therapy;Francisella tularensis
Report Number
DRDC-SUFFIELD-SL-2002-143 — Scientific Literature
Date of publication
01 Jul 2003
Number of Pages
10
Reprinted from
Journal of Controlled Release, vol 92, 2003, p 265-273
DSTKIM No
CA024479
CANDIS No
522063
Format(s):
Hardcopy;Document Image stored on Optical Disk

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