Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes.

In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into liposomes (CPFX-liposomes) for treatment of respiratory intracellular parasite infections, the influence of particle size on drug delivery to rat alveolar macrophages (AMs) following pulmonary administration of CPFX-liposomes was investigated. CPFX-liposomes were prepared with hydrogenated soybean phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five different particle sizes (100, 200, 400, 1000 and 2000 nm). In the pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following pulmonary administration of CPFX-liposomes increased with the increase in the particle size over the range 100-1000 nm and became constant at over 1000 nm. The concentrations of CPFX in rat AMs until 24 h after pulmonary administration of CPFX-liposomes with a particle size of 1000 nm were higher than the minimum inhibitory concentration of CPFX against various intracellular parasites. In a cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues by pulmonary administration of CPFX-liposomes with a particle size of 1000 nm was observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX-liposomes with a particle size of 1000 nm induces an excellent antibacterial effect without any cytotoxic effects on lung tissues. Therefore, CPFX-liposomes may be useful in the development of drug delivery systems for the treatment of respiratory infections caused by intracellular parasites, such as Mycobacterium tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.