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Amantadine Amides Prodrugs as Hepatic Delivery Systems to Enhance its Activity Against HCV

مؤلف البحث
Tarek Aboul-Fadl, Mahmoud M. Sheha, Adel S. El-Azab, Hatem A. Abdel-Aziz
مجلة البحث
Digest Journal of Nanomaterials and Biostructures
الناشر
the Academy of Romanian Scientists
تصنيف البحث
1
عدد البحث
Vol. 6, No. 4
موقع البحث
http://www.chalcogen.infim.ro/1675_Fadl.pdf
سنة البحث
2011
المشارك في البحث
ملخص البحث

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°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.