Therapy of Mycobacterium avium complex infections in beige mice with streptomycin encapsulated in sterically stabilized liposomes

Abstract

Mycobacterium avium complex (MAC) causes serious opportunistic infections in AIDS patients. Previous studies with MAC-infected beige mice have indicated that weekly administration of liposome-encapsulated streptomycin can reduce significantly the CFU in the liver and spleen. We examined whether streptomycin encapsulated in recently developed sterically stabilized liposomes with prolonged circulation times would have a therapeutic effect in this animal model. Two liposome types with prolonged circulation (polyethyleneglycol-distearoylphosphatidylethanolamine [PEG-DSPE]-distearoylphosphatidylcholine [DSPC]-cholesterol [chol] or phosphatidylinositol [PI]-DSPC-chol) and conventional liposomes (phosphatidylglycerol [PG]-phosphatidylcholine [PC]-chol) encapsulating streptomycin and administered twice weekly were bactericidal to MAC strain 101 in the spleen when the level of infection after treatment was compared with the level of infection before treatment. PI-DSPC-chol and PG-PC-chol liposomes encapsulating streptomycin were bactericidal in the liver. Although PG-PC-chol or PEG-DSPE-DSPE-chol liposomes encapsulating streptomycin were not bactericidal in the lungs, they reduced the level of MAC infection by more than 3 orders of magnitude compared with the level of MAC infection in untreated controls.