Liposomal Formulation Increases Local Delivery of Amphotericin from Bone Cement: A Pilot Study

Abstract

Amphotericin is a highly toxic hydrophobic antifungal. Delivery of amphotericin from antifungal-loaded bone cement (ALBC) is much lower than would be expected for an equivalent load of water-soluble antibacterials. Lipid formulations have been developed to decrease amphotericin toxicity. It is unknown how lipid formulations affect amphotericin release and compressive strength of amphotericin ALBC. We asked if amphotericin release from liposomal amphotericin ALBC (1) changed with amphotericin load; (2) differed from release from amphotericin deoxycholate ALBC; (3) was an active drug; and (4) if liposomal amphotericin affected the bone cement strength. Forty-five standardized test cylinders were fabricated from three formulations of ALBC: Simplex™ P bone cement with 200 mg liposomal amphotericin, 800 mg liposomal amphotericin, or 800 mg amphotericin deoxycholate per batch. For each ALBC formulation, cumulative released amphotericin was determined from five cylinders, and compressive strength was measured for 10 cylinders, five before elution and five after. Activity of released amphotericin was determined by growth inhibition assay. Amphotericin release was greater for increased load of liposomal amphotericin: 770 μg for 800 mg versus 118 μg for 200 mg. Amphotericin release was greater from liposomal ALBC than from deoxycholate ALBC: 770 μg versus 23 μg over 7 days for 800 mg amphotericin. Released amphotericin was active. Compressive strength of liposomal ALBC is decreased, 67 MPa and 34 MPa by Day 7 in elution for the 200-mg and 800-mg formulations, respectively. Liposomal amphotericin has greater amphotericin release from ALBC than amphotericin deoxycholate. Compressive strength of liposomal amphotericin ALBC decreases to less than recommended for implant fixation. Local toxicity data are needed before liposomal amphotericin ALBC can be used clinically.