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Liposomal amikacin: improved treatment of Mycobacterium avium complex infection in the beige mouse model
E A Petersen1, J B Grayson, E M Hersh
1Department of Medicine, University of Arizona College of Medicine, Tucson, USA.
Abstract:
Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4 degrees C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 10(7) cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.
Insights
A novel liposomal amikacin (VS107) formulation effectively treats disseminated Mycobacterium avium complex (MAC) infections in mice. This advanced drug delivery system significantly reduces bacterial load and improves survival, offering a promising therapeutic option for AIDS patients.
Area of Science:
- Pharmacology
- Infectious Diseases
- Drug Delivery Systems
Background:
- Disseminated Mycobacterium avium complex (MAC) infections are a significant threat to AIDS patients.
- Existing treatments face challenges in efficacy and patient outcomes.
Purpose of the Study:
- To develop and evaluate a liposomal amikacin preparation (VS107) for treating MAC infections.
- To assess the microbiological, pharmacological, and therapeutic efficacy of VS107 in a mouse model.
Main Methods:
- Development of VS107: amikacin encapsulated in 54-65 nm unilamellar liposomes.
- Pharmacokinetic studies in mice to determine serum half-life and peak levels.
- Therapeutic efficacy assessed in beige mice infected with M. avium, comparing VS107 to free amikacin and placebo.
Main Results:
- VS107 demonstrated superior microbiological activity compared to conventional amikacin.
- Significantly lower viable M. avium counts in the liver and spleen of VS107-treated mice.
- VS107 treatment led to improved survival rates in the infected mouse model.
Conclusions:
- Liposomal amikacin (VS107) shows enhanced efficacy and tolerability for MAC infections.
- VS107 represents a potentially valuable therapeutic candidate for human MAC infections.