PHYSICOCHEMICAL CHARACTERIZATION OF BISPHOSPHONIC CARBOXYFLUORESCEIN FOR OSTEOTROPIC DRUG-DELIVERY

Disodium (fluorescein-6-carbonyloxy)acetoaminomethylene bisphosphonate (CF-BP), a prodrug of 6-carboxyfluorescein, is efficiently absorbed b y the skeleton where it hydrolyses to carboxyfluorescein. An osteotrop ic drug-delivery system based on this bisphosphonic prodrug has been d eveloped as a novel method for site-specific and controlled delivery o f drugs to the bone. In this study the physicochemical properties of t he prodrug have been characterized by investigating the affinity of CF -BP for hydroxyapatite and the hydrolysis of the compound to carboxyfl uorescein. In the binding study, CF-BP bound very rapidly to hydroxyap atite without degradation and carboxyfluorescein was subsequently grad ually released by hydrolysis of bound CF-BP. Hydrolysis of CF-BP in bu ffer solutions followed pseudo-first-order kinetics, and quantitative regeneration of carboxyfluorescein was observed. In addition, regenera tion of carboxyfluorescein from CF-BP was accelerated in the presence of fresh rat plasma. These results suggest that CF-BP has the physicoc hemical properties required for site-specific and controlled delivery of carboxyfluorescein to bones.