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Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection

Item Type:Article
Title:Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection
Creators Name:Peters, K. and Leitzke, S. and Diederichs, J.E. and Borner, K. and Hahn, H. and Mueller, R.H. and Ehlers, S.
Abstract:Clofazimine nanosuspensions were produced by high pressure homogenization and the formulation was optimized for lyophilization. Characterization of the product by photon correlation spectroscopy, laser diffraction and Coulter counter analysis showed that the clofazimine nanosuspensions were suitable for iv injection with a particle size permitting passive targeting to the reticuloendothelial system. Following iv administration to mice of either the nanocrystalline or a control liposomal formulation at a dose of 20 mg clofazimine/kg bodyweight, drug concentrations in livers, spleens and lungs reached comparably high concentrations, well in excess of the MIC for most Mycobacterium avium strains. When C57BL/6 mice were experimentally infected with M. avium strain TMC 724, nanocrystalline clofazimine was as effective as liposomal clofazimine in reducing bacterial loads in the liver, spleen and lungs of infected mice. Nanocrystalline suspensions of poorly soluble drugs such as riminophenazines are easy to prepare and to lyophilize for extended storage and represent a promising new drug formulation for intravenous therapy of mycobacterial infections.
Keywords:Animal Disease Models, Anti-Bacterial Agents, Clofazimine, Drug Carriers, Freeze Drying, Inbred C57BL Mice, Intravenous Infusions, Liposomes, Mycobacterium Avium, Mycobacterium Avium-Intracellulare Infection, Suspensions, Animals, Mice
Source:Journal of Antimicrobial Chemotherapy
ISSN:0305-7453
Publisher:Oxford Univ Press (England)
Volume:45
Number:1
Page Range:77-83
Date:1 January 2000
Official Publication:http://jac.oxfordjournals.org/cgi/content/abstract/45/1/77
PubMed:View item in PubMed

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