Gallic acid-PAMAM and gallic acid-phospholipid conjugates, physicochemical characterization and in vivo evaluation

Gallic acid (GA) is a naturally occurring compound with valuable antioxidant activity. Its oral bioavailability is limited by its high metabolism and rapid clearance. In this paper, GA was conjugated with two different materials, phosphatidylcholine (PC) and polyamidoamine (PAMAM) dendrimer. The prepared conjugates were characterized by FTIR, DSC, and SEM. Also, they were tested for drug content and in vitro drug release. It was found that GA conjugation with both materials have significantly prolonged its release up to 12h. In vivo hepatoprotective activity of free and conjugated GA was studied in rats after carbon tetrachloride (CCl4)-induced oxidative damage in rat liver through measurement of different liver marker enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT)), in addition to the total protein and albumin level in rat serum. Also, histopathological examination of liver cell of all rat groups was done. Results showed that both prepared conjugates have significantly reduced the hepatic marker enzymes accompanied by normalizing total protein and albumin levels in rat serum and with respect to CCl4-induced group (p<.05). Histopathological examination showed that pretreatment of rats with GA-PC or GA-PAMAM before CCL4 could reduce the induced cellular histopathological changes. It appears that conjugation of GA could enhance its bioavailability and increase its hepatoprotective effect.