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Several respiratory infections are frequently induced by pathogenic microorganisms in lung epithelial lining fluid (ELF) and alveolar macrophages (AM). Then, two studies concerning designs of antimicrobial therapy systems of respiratory infections were carried out; one was the distribution mechanisms of three macrolide and ketolide antibiotics, clarithromycin (CAM), azithromycin (AZM) and telithromycin (TEL) in plasma, ELF and AM, and the other was the efficient drug delivery to AM by pulmonary administration of fluoroquinolone antibiotic, a ciprofloxacin (CPFX) incorporated into liposomes (CPFX-liposome). In the first study, the areas under drug concentration-time curves (AUCs) in ELF following oral administration of three macrolide and ketolide antibiotics to rats were significantly higher than AUCs in plasma, furthermore AUCs in AM significantly higher than AUCs in ELF. The high distribution of these antibiotics to the respiratory infection site is due to the transport from blood to ELF via MDR1 in lung epithelial cells as well as the uptake by AM. These antibiotics were taken up by AM via active transport system and the trapping in organelles. In the second study, drug delivery efficacy of CPFX-liposome to AM was particle size-dependent over the 100-1000 nm and then become constant at over 1000 nm by pulmonary aerosolization to rats. This result indicates that the most effective size is 1000 nm. Furthermore, the drug delivery efficacy of mannosylated CPFX-liposome (particle size: 1000 nm) was highly delivered to AM and antibacterial effects were significantly higher than those of unmodified CPFX-liposome. This review provides useful findings for microbial therapy systems of respiratory infections.

Designs of Optimized Microbial Therapy Systems of Respiratory Infections