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Improving Anti-Cancer Potentiality and Bioavailability of Gallic Acid by Designing Polymeric Nanocomposite Formulation
Asian Pacific Journal of Cancer Prevention : APJCP 2018 November 30
Objective: In this study, we investigated the in vivo antitumor activity and pharmacokinetic characteristics of encapsulated GA-NC (gallic acid nanocomposite) in normal and hepatocellular carcinoma (HCC)-induced rats. Methods: Rats were distributed into 4 groups; negative control, HCC, gallic acid (GA), and GA-NC. Serum levels of alpha-fetoprotein (AFP), endoglin (ENG), heat shock protein-70 (HSP-70), pro-caspase 3, lipocalin-2 (LCN-2) and β-cell leukemia/lymphoma 2 (Bcl-2) were assayed by ELISA. The pharmacokinetic parameters for GA or GA-NC were determined by means of non-compartmental approach based on the serum– concentration profiles of free GA and GA-NC after oral administration. Also, histological procedures were used for examination of liver tissue sections. Results: Anaplastic changes in liver tissues were observed in untreated HCC group, as well as a significant increase in the serum AFP level. In addition, significant elevation in the serum ENG level as an angiogenic marker and the serum levels of the apoptotic mediators; HSP-70, Bcl-2 and pro-caspase 3 beside significant amplification in the serum inflammatory modulator, LCN-2 were recorded. Treatment with free GA or GA-NC markedly recovered the anaplastic changes in the rat liver tissues. In addition, they restored serum levels of AFP, ENG, HSP-70, Bcl-2, pro-caspase-3, and LCN-2. Pharmacokinetic analysis revealed that GA–NC displayed a characteristic sustained release profile with 4-fold increase in bioavailability in normal and HCC-induced rats. Conclusions: The results of this study suggest that encapsulation of GA into PLGA-CS-PEG enhances its oral bioavailability and anti-cancer activity. GA-NC may be a new therapeutic candidate for the mitigation of hepatocarcinogenesis.
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