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

Clofazimine nanosuspensions were produced by high pressure homogenization a nd the formulation was optimized for lyophilization. Characterization of th e 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 t he nanocrystalline or a control liposomal formulation at a dose of 20 mg cl ofazimine/kg bodyweight, drug concentrations in livers, spleens and lungs r eached comparably high concentrations, well in excess of the MIC for most M ycobacterium 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 a nd lungs of infected mice. Nanocrystalline suspensions of poorly soluble dr ugs such as riminophenazines are easy to prepare and to lyophilize for exte nded storage and represent a promising new drug formulation for intravenous therapy of mycobacterial infections.