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 micrograms/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 micrograms/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 micrograms/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.
Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
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Gomez-Flores
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Tamez-Guerra
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Mehta
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004339:Drug Compounding; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015269:Mycobacterium avium Complex / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D008081:Liposomes; C058733:resorcinomycin A