Hydroxyapatite crystals as a local delivery system for cisplatin: adsorption and release of cisplatin in vitro

Abstract

This study describes the characteristics of the in vitro binding and release of the anti-tumor drug cisplatin by slurries of synthetic hydroxyapatite crystals carried out in aqueous media. The adsorption of cisplatin by slurries of hydroxyapatite and its release were found to depend significantly on the ionic composition of the aqueous media used. At a constant pH of 7.4, significantly more cisplatin is adsorbed by the hydroxyapatite crystals in the slurry from a chloride-free phosphate buffered solution or a Tris buffered solution than from a buffered phosphate solution containing chloride ions. The amount of hydroxyapatite-bound cisplatin desorbed into solution was also progressively increased as a function of the increasing concentration of chloride in the equilibrating solution. Very little hydroxyapatite-bound cisplatin was released from the crystals in either a Tris or phosphate buffer. These results suggest that it is the hydrated derivatives of cisplatin which are involved in the adsorption of cisplatin by hydroxyapatite crystals. The adsorption data can be expressed as a Freundlich isotherm from which the association constant can be calculated. The rate of release of cisplatin bound to crystals of hydroxyapatite is relatively slow even at the maximum concentration of chloride ions in the phosphate buffer. Approximately 33% of the total cisplatin bound to the crystals of hydroxyapatite was released after 4.25 days. An additional 15% of the remaining cisplatin bound to the hydroxyapatite cyrstals was released after an additional equilibration with fresh buffer for two weeks (58% of the total cisplatin originally bound). These findings suggest that cisplatin bound to slurries of hydroxyapatite crystals may be useful in the local treatment of malignant tumors.