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

Abstract

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.

Antibacterial Efficacy of Inhalable Levofloxacin-Loaded Polymeric Nanoparticles Against E. coli Biofilm Cells: The Effect of Antibiotic Release Profile

“…As a result, the antibiotic is released locally, therefore increasing its residence time and concentration in the biofilm infection sites, which leads to a higher antibacterial efficacy than that obtained by the free-drug formulation (11,13). In addition, nanoparticles have been found to exhibit a longer retention time in the lung compared to their micron-scale particle counterparts, as the lung macrophages are less effective in recognizing foreign particles smaller than 1-2 µm (14).…”

Nanomedicine in pulmonary delivery

“…Although the upper limit of particle size for ophthalmic application is about 5 µm, the optimum particle size is less than 1,000 nm because a scratching feeling can occur when microparticles are applied to the eyes. 12 Phagocytosis is sensitive to particle size, and it is generally thought that particles of 0.5-3 µm in diameter are taken up by macrophages, 13 and particles of less than 0.26 µm can escape from phagocytosis by macrophages. 1 Phagocytosis is also the main mechanism responsible for the rapid clearance of particulate drug delivery systems from the body.…”

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

“…Another unique property of NPs is the tendency to be phagocytized by alveolar macrophages, if they are in the range of 500–3000 nm [75,76]. The simultaneous effects, of NPs uptake and release, were demonstrated simultaneously, when a study of multilamellar liposomes containing rifampicin and isoniazid exhibited presence in alveolar macrophages and could maintain therapeutic concentrations in the lung tissue for 5 days [77].…”