Enhanced intramacrophage activity of resorcinomycin A against Mycobacterium avium Mycobacterium intracellulare complex after liposome encapsulation

The activities of free and liposomal resorcinomycin A against Mycobacterium avium-Mycobacterium intracellulare complex (MAC) grown in broth and in murine peritoneal macrophages were evaluated, Liposomal resorcinomycin A was composed of dimyristoyl phosphatidylcholine and phosphatidylinositol at a molar ratio of 9:1, Both free resorcinomycin A and liposomal resorcinomycin A showed no toxicity to macrophages at concentrations up to 50 mu g/ml, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, Minimal inhibitory concentrations of free resorcinomycin A and liposomal resorcinomycin A in broth were 6 and 12 mu g/ml, respectively, as determined by the MTT colorimetric microassay, In macrophages, liposomal resorcinomycin A caused significantly higher intramacrophage antimycobacterial activity than the free form of the drug, At doses ranging from 6 to 50 mu g/ml, liposomal resorcinomycin A caused 50 to 93% MAC growth inhibition, respectively (as determined by CFU), while free resorcinomycin A was associated with 33 to 62% MAC growth inhibition, respectively, 3 days after drug treatment, In addition, antimycobacterial activity of liposomal resorcinomycin A in macrophages was maintained 7 days after treatment, whereas the activity of free resorcinomycin A was reduced to negligible 3 days after treatment, In summary, liposome encapsulation of resorcinomycin A resulted in significant enhancement of antibacterial activity against intramacrophagic MAC infection.