NOVEL ANTIFUNGAL DRUG DELIVERY - STABLE AMPHOTERICIN B-CHOLESTERYL SULFATE DISKS

To improve the clinical utility of a potent fungicidal agent, amphotericin B (AB), we developed a novel drug dosage form based on the specific interaction of AB with sterols. AB and sodium cholesteryl sulfate at an equimolar ratio form a thermodynamically stable discoidal complex of uniform size. The therapeutic index of the drug is significantly improved (4-6-fold) as a direct result of the unique physical properties of this colloidal system. This drug/lipid complex does not hemolyze red blood cells, exhibits only low binding to plasma lipoproteins in vitro, alters plasma kinetics and tissue distribution compared to a deoxycholate/AB micellar formulation, and is effective in eradicating fungal infections in vivo.