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

Abstract

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 12 h. 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.

Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted β-Sitosterol against CCl4 induced hepatotoxicity in rats

“…On the seventh day, a single dose of a mixture of CCl 4 and olive oil (1:1) was given (50% v/v, 2 mL/kg, i.p.) 36 to all animals except those in the normal group.…”

The Role of Branch Cell Symmetry and Other Critical Nanoscale Design Parameters in the Determination of Dendrimer Encapsulation Properties

“…Resveratrol PAMAM hybrid Improved solubility [172] Resveratrol is a stilbene compound known for its anti-oxidant/anti-ageing properties that suffers from poor water solubility [172] developed a G4, PAMAM dendrimer formulation for transdermal applications with improved water solubility, stability and skin penetration. Gallic Acid PAMAM conjugation Improved bioavailability [173] 4.1.6. Anti-Microbial Drugs Table 6.…”

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies

“…It is now contended that conjugation of drugs with fatty acids not only provides enhanced targeted drug delivery to the tumor but also enhances anticancer activities, as fatty acids are highly taken up by a tumor. For instance, omega-3 fatty acid, docosahexaenoic acid (DHA), is readily taken up by tumor cells, and hence, provides reduced tumor growth [ 42 ]. Thus, in order to enhance the anticancer activities of paclitaxel, DHA was conjugated to the synthesized amine terminated PAMAM-G4 dendrimer to provide a PAMAM-G4-DHA-PTX and PAMAM-G4-PTX drug conjugates [ 37 ].…”

“…Efforts to increase the bioavailability of gallic acid have been attempted by various research groups. Abduo and Masoud evaluated bioavailability of gallic acid by conjugating it to PAMAM dendrimer and phosphatidylcholine (PC) [ 42 ]. Both systems, PAMAM and PC sustained the release of gallic acid for several hours compared to the free one.…”

“…Both systems, PAMAM and PC sustained the release of gallic acid for several hours compared to the free one. Furthermore, gallic-PAMAM and gallic-PC conjugate improved bioavailability, provided hepatoprotection thereby improving the histological appearance of liver cells [ 42 ]. Conjugation of gallic acid to PAMAM or PC thus provided a means to improve its bioavailability…”