Monitoring safety of liposomes containing rifampicin on respiratory cell lines and in vitro efficacy against Mycobacterium bovis in alveolar macrophages.
Rifampicin-encapsulated liposome suspensions were prepared by a chloroform-film method and converted to dry powders by freeze-drying with mannitol as a cryoprotectant. The liposome suspension had multilamellar nanovesicles with 50% rifampicin encapsulation. The liposome dry powder comprised particles with a mass median aerodynamic diameter of 3.4 mum, with 60% present as a fine particle fraction. Rifampicin-encapsulated liposomes were evidently nontoxic to respiratory associated cells, including bronchial epithelial cells, small airway epithelial and alveolar macrophages (AMs). Furthermore, the liposomes did not activate AMs to produce interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide at a level that would cascade to other inflammatory effects. The minimum inhibitory concentrations against Mycobacterium bovis was 0.2 and 0.8 microM for liposomes containing rifampicin and free rifampicin, respectively. The less negatively charged reconstituted liposome displayed the greatest activity against intracellular growth of M. bovis.
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkhla, Thailand.
Narumon
N
Changsan
Athip
A
Nilkaeo
Pethchawan
P
Pungrassami
Teerapol
T
Srichana
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D003451:Cryoprotective Agents / Q000737:chemistry; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005612:Freeze Drying; D006801:Humans; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000382:microbiology; D008353:Mannitol / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009163:Mycobacterium bovis / Q000187:drug effects*; D010316:Particle Size; D011208:Powders; D051381:Rats; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
D000904:Antibiotics, Antitubercular; D003451:Cryoprotective Agents; D008081:Liposomes; D011208:Powders; D008353:Mannitol; D012293:Rifampin