Physicochemical characterization of bisphosphonic carboxyfluorescein for osteotropic drug delivery

Article abstract of DOI:10.1111/j.2042-7158.1996.tb03976.x

Disodium (fluorescein-6-carbonyloxy)acetoaminomethylene bisphosphonate (CF-BP), a prodrug of 6-carboxyfluorescein, is efficiently absorbed by the skeleton where it hydrolyses to carboxyfluorescein. An osteotropic drug-delivery system based on this bisphosphonic prodrug has been developed as a novel method for site-specific and controlled delivery of drugs to the bone. In this study the physicochemical properties of the prodrug have been characterized by investigating the affinity of CF-BP for hydroxyapatite and the hydrolysis of the compound to carboxyfluorescein. In the binding study, CF-BP bound very rapidly to hydroxyapatite without degradation and carboxyfluorescein was subsequently gradually released by hydrolysis of bound CF-BP. Hydrolysis of CF-BP in buffer solutions followed pseudo-first-order kinetics, and quantitative regeneration of carboxyfluorescein was observed. In addition, regeneration of carboxyfluorescein from CF-BP was accelerated in the presence of fresh rat plasma. These results suggest that CF-BP has the physicochemical properties required for site-specific and controlled delivery of carboxyfluorescein to bones.