AMANTADINE AMIDES PRODRUGS AS HEPATIC DELIVERY SYSTEMS TO ENHANCE ITS ACTIVITY AGAINST HCV

作者：Aboul Fadl Tarek^*; Sheha Mahmoud M; El Azab Adel S; Abdel Aziz Hatem A

来源：Digest Journal of Nanomaterials and Biostructures, 2011, 6(4): 1675-1683.

• Amantadine
• HCV
• Hepatic delivery system
• Prodrug
• Thiazolidine-carboxylic acdis
• Bile acids

To enhance the activity of amantadine against HCV, its amide prodrugs with thiazolidine-4-carboxylic acid derivatives (6-9) and bile acids (10 and 11) were designed and synthesized. In vitro kinetic stability of amide prodrugs 8 and 10 were investigated in aqueous buffer solution with variable pH values (1.2, 4.5. 6.8, 7.4. 8.0) and in biological fluids of 90% human plasma and rat liver homogenate at 37 degrees C. In vivo release of the parent drug from these prodrug was investigated in mice with the thioazolidine-4-carboxylic acid amide 8 as representative of these delivery systems. Results from the in vivo distribution study indicated that the level of amantadine increased significantly in liver from 8 when compared to amantadine itself. The study suggested the synthesized delivery systems is promising carrier to enhance the hepatic bioavailability of amantadine.

• 出版日期2011-12