Improving Anti-Cancer Potentiality and Bioavailability of Gallic Acid by Designing Polymeric Nanocomposite Formulation

Hanaa Ahmed,Ahmed A Abd-Rabou,Fathy M Mehaya,Aziza B Shalby,Asmaa F Galal

doi:10.31557/apjcp.2018.19.11.3137

Hanaa Ahmed, Ahmed A Abd-Rabou + Show 3 more

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https://doi.org/10.31557/apjcp.2018.19.11.3137

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Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is considered as the third main cause of cancer-related mortality
In this study, we investigated the in vivo antitumor activity and pharmacokinetic characteristics of encapsulated gallic acid (GA)-NC in normal and hepatocellular carcinoma (HCC)-induced rats
The present study proposed GA encapsulated in PLGA-CS-PEG as a new GA-based therapy for HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is considered as the third main cause of cancer-related mortality. In Egypt, HCC is the second recorded cancer type in men and the sixth type in women (Ziada et al, 2016). Several treatment strategies are available for HCC like curative resection, radiofrequency ablation, liver transplantation, radioembolization and systemic targeted chemotherapy (Samarakoon et al, 2017). Chemotherapy causes survival of HCC patients with severe adverse events such as diarrhea, hand-foot skin disease, fatigue, anorexia and alopecia (Kumar et al, 2016). The development of multidrug resistance (MDR) to chemotherapy becomes an obstacle facing HCC therapy. Those serious side effects encourage searching for new anticancer agents for HCC with fewer adverse effects (Liang et al, 2010)

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