Document Type: Research Articles
Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt.
Narcotics, Ergogenics and Poisons Department, National Research Centre, Giza, Egypt.
Department of Food Technology, National Research Centre, Giza, Egypt.
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.