Physicochemical characterization of bisphosphonic carboxyfluorescein for osteotropic drug delivery

被引:11
作者
Fujisaki, J
Tokunaga, Y
Takahashi, T
Murata, S
Shimojo, F
Hata, T
机构
[1] Pharmaceutical Pharmacokinetic R., Fujisawa Pharmaceutical Company Ltd., Kashima, Yodogawa-ku, Osaka 532, 1-6
关键词
D O I
10.1111/j.2042-7158.1996.tb03976.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:798 / 800
页数:3
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