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Journal of Antimicrobial Chemotherapy (1993) 31, 569-579
© 1993 The British Society for Antimicrobial Chemotherapy

other

Liposomal hamycin in the control of experimental aspergillosis in mice: effect of phosphatidic acid with and without cholesterol

Mona Moonis, Imran Ahmad* and Bimal Kumar Bachhawat

Department of Biochemistry, Liposome Research Centre, University of Delhi South Campus, New Delhi-110021, India

Received 28 May 1992; accepted 23 November 1992

*Present address: Department of Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Canada T6G 2H7

Hamycin incorporated into liposomes containing phosphatidyicholine (SPC) and phosphatidic acid (PA) had reduced toxicity and an enhanced antifungal activity in experimental aspergillosis in balb/c mice. Incorporation of cholesterol into liposomes led to a dose dependent decrease in the toxicity of hamycin. The LD50 (mg/kg) of hamycin contained in SPC/cholesterol/PA (molar ratio 4: 5: 1) liposomes was 2.8 whereas that in SPC/PA liposomes (molar ratio 9:1) was 0.35 Although the free drug had little or no protective effect on the animals, those administered liposomal hamycin at an equivalent dose (0.1 mg/kg) in the absence of cholesterol (SPC/PA; molar ratio 9:1) showed 90% survival after seven days of therapy. On the other hand the presence of cholesterol in the carrier phosphatidic acid liposomes (SPC/ cholesterol/PA; molar ratio 4:5:1) at a similar dose (0.1 mg/kg) led to a 60% survival over the same time period. Hamycin incorporation in phosphatidic acid liposomes both in the presence or absence of cholesterol was found to be effective in reducing the fungal load in lung, liver, spleen and kidney. Studies with distribution of hamycin in various tissues by HPLC showed a significant reduction in the concentration of the liposomal drug in circulation as compared to those seem after administration of free drug.


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