Enhanced effect of liposome-encapsulated amikacin on Mycobacterium avium-M. intracellulare complex infection in beige mice

We examined the therapeutic effects of free and liposome-encapsulated amikacin on Mycobacterium avium-M. intracellulare complex infection by using the beige-mouse model of the disease. In the first series of studies, intravenous administration of four weekly doses of 5 mg of amikacin per kg encapsulated in large (approximately 0.4-μm diameter), unilamellar liposomes arrested the growth of M. avium-M. intracellulare complex organisms in the liver, as measured by CFU counts. M. avium-M. intracellulare complex levels in untreated animals and in those treated with the same dose of free amikacin increased by several orders of magnitude over 8 weeks. Liposome-encapsulated amikacin was also effective against M. avium-M. intracellulare complex organisms in the spleens and kidneys, reducing the CFU counts by about 1,000-fold compared with those of both untreated controls and free-drug-treated mice. In the lungs, a slight reduction in CFU was observed in the liposome-encapsulated-amikacin-treated group, but only at the 8-week point. Neither free nor liposome-encapsulated amikacin reduced the colony counts in the lymph nodes compared with those of control animals. Reductions in CFU in all organs greater than those caused by the liposome preparation could be achieved by intramuscular administration of free amikacin, but only at a 10-fold-higher dose given 6 days a week for 8 weeks. In the second series of studies, we investigated the effects of (i) doubling the dose of liposome-encapsulated amikacin and (ii) increasing the size of the liposomes and prolonging the treatment to five injections. Administration of 10 mg of amikacin per kg in liposomes 2 to 3 μm in diameter was more effective in the liver than 5 or 10 mg of amikacin per kg in liposomes 0.2 μm in diameter. A slight reduction in the CFU levels in the lungs was observed with the higher dose, irrespective of liposome size. Our results indicate that liposome-based delivery of amikacin enhances its anti-M. avium-M. intracellulare complex activity, particularly in the liver, spleen, and kidney, and may therefore improve the therapy of this disease

Differential effects of free and liposome encapsulated amikacin on the survival of Mycobacterium avium complex in mouse peritoneal macrophages

Liposome-encapsulated amikacin shows significantly greater inhibitory activity against the survival of Mycobacterium avium complex inside mouse peritoneal macrophages than the free drug. Similar results were obtained whether the drug was added simultaneously with, 48 h prior to, or 48 h after the addition of mycobacteria to the macrophages. These observations support the hypothesis that the in vivo intravenous delivery of liposome-encapsulated amikacin results in the localization of the antibiotic in phagosomes containing mycobacteria inside resident macrophages of the liver and spleen. © 1990

Chemotherapeutic potential of free and liposome encapsulated streptomycin against experimental mycobacterium avium complex infections in beige mice

We investigated in two experiments the chemotherapeutic role of streptomycin on the progression of Mycobacterium avium complex (MAC) disease in beige mice. In the first experiment, streptomycin 100 mg/kg given intramuscularly (im) five days a week for four weeks caused a significant reduction of the colony forming unit (cfu) counts of MAC from spleen, lungs and liver. In the same experiment, streptomycin, given in an encapsulated form in multilamellar liposomes at 15 mg/kg in two intravenous (iv) injections caused greater reduction of cfu in the three tissues. In the second experiment, the effect of free streptomycin at 150 mg/kg given im five days a week for eight weeks was compared with 15 mg/kg of streptomycin encapsulated in unilamellar liposomes given iv in four injections (one day and at three weekly intervals) with no further treatment within the eight weeks. Similar results as in the first experiment were obtained. In both experiments, liposome encapsulation resulted in several-fold increase in the chemotherapeutic efficacy when the data was expressed as reduction of cfu counts per unit dose of the drug. © 1991, by The British Society for Antimicrobial Chemotherapy