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+/-3.5%. Following administration of unencapsulated or
liposome-encapsulated
ciprofloxacin by
intravenous injection or
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 inhalation of
liposome-encapsulated
ciprofloxacin, given either prophylactically or therapeutically, provided complete protection to 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 encapsulation of
ciprofloxacin enhances
drug delivery to the primary site of
infection and results in increasing therapeutic efficacy against F. tularensis.