R. Gomezflores et al., ENHANCED INTRAMACROPHAGE ACTIVITY OF RESORCINOMYCIN A AGAINST MYCOBACTERIUM-AVIUM MYCOBACTERIUM-INTRACELLULARE COMPLEX AFTER LIPOSOME ENCAPSULATION, Antimicrobial agents and chemotherapy, 40(11), 1996, pp. 2545-2549
The activities of free and liposomal resorcinomycin A against Mycobact
erium avium-Mycobacterium intracellulare complex (MAC) grown in broth
and in murine peritoneal macrophages were evaluated, Liposomal resorci
nomycin A was composed of dimyristoyl phosphatidylcholine and phosphat
idylinositol at a molar ratio of 9:1, Both free resorcinomycin A and l
iposomal resorcinomycin A showed no toxicity to macrophages at concent
rations up to 50 mu g/ml, as determined by the (4,5-dimethylthiazol-2-
yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, Minimal inh
ibitory concentrations of free resorcinomycin A and liposomal resorcin
omycin A in broth were 6 and 12 mu g/ml, respectively, as determined b
y the MTT colorimetric microassay, In macrophages, liposomal resorcino
mycin 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 inhib
ition, 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 encapsulati
on of resorcinomycin A resulted in significant enhancement of antibact
erial activity against intramacrophagic MAC infection.