Targeted and Controlled Release of Indomethacin from a Prodrug of Amylose
会议名称：《第七届亚太地区医学与生物学工程学术年会》
会议日期：2008年
学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学]
基 金：the National Natural Science Foundation of China (20574089, 20676155) the Scientific Research Foundation for the Returned Overseas Chinese Scholars from the State Education Ministry
关 键 词：Prodrug Amylose Indomethacin Release
摘 要：A series of prodrugs of amylose grafted with in-domethacin （IND） were mildly synthesized at room tempera-ture and their chemical structures were characterized by FTIR and 1H NMR spectroscopy. The results showed that IND was conjugated with amylose through the ester bond. The loaded IND content in each prodrug was determined to be 1.8, 2.7, 4.8, 12.0, 15.6 and 21.6 mg/g from UV spectroscopy. For in vitro experiment, the simulated medium for stomach and small intestine was a chloric acid solution （pH 1.2）, and a sodium phosphate buffer solution （pH 6.8） containing porcine pan-creatin. A culture fermentation system was used to simulate the colonic condition. The results indicated that IND was hardly released in the simulated stomach medium, but could be controlled released by hydrolysis of the prodrug through α-amylase and lipase in the simulated small intestine and colonic conditions. The pharmacokinetic analysis indicated that Tmax, the time at which a maximum concentration of drug in the plasma, was 2.1 h for free IND. But it was prolonged to 5.2 - 8.8 h for the prodrugs. Meanwhile, the maximum drug concentration in the plasma （Cmax） decreased from 25.8 μg/mL for free IND to 0.5 - 7.0 μg/mL for the prodrugs. It further proved that the prodrug could realize controlled release IND.