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

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.

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

“…Similar results were obtained also in case of PCA-ZnAL [26]. As well as in Fe 3 O 4 -PEG-GA [46] and PLGA-CS-PEG used to encapsulate GA [47]. Encapsulation of FE into cyclodextrin nanosponges led to improved solubility and cytotoxicity [80].…”

“…Similarly, as in case of GeA, iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with GA (Fe 3 O 4 -PEG-GA) were found to be more effective against human lung A549, breast MCF-7, and colon HT-29 cells when compared with free GA [46]. Moreover, encapsulation of GA into PLGA-CS-PEG nanocomposite was also associated with increase in its bioavailability and antitumor efficacy in rats [47].…”

Development of a Fast, Low‐Cost, Conservative and Ecological Method for Quantifying Gallic Acid in Polymeric Formulations by FTIR Spectroscopy in Solution

“…In the last decade, several natural or synthetic polymers, including acryloyldimethyl taurate with propylene glycol, polylactic‐co‐glycolic acid (PLGA), polyethylene glycol (PEG), chitosane, cyclodextrins, dextrane and dendrimers such as poly(amidoamine) (PAMAM) or polyester‐based ones have emerged as promising carrier systems for GA.…”

Traditional Tibetan Medicine in Cancer Therapy by Targeting Apoptosis Pathways

“…Gallic acid, 3,4,5-trihydroxybenzoic acid ( Figure 3 ), which can be found in various natural products, such as green tea, grapes, Punica granatum L., P. emblica , Galla chinensis Mill., and many other fruits plants. Gallic acid known to affect several pharmacological and biochemical pathways have strong antioxidant, antimutagenic, anti-inflammatory, and anticancer properties ( Karimi-Khouzani et al., 2017 ; Limpisophon and Schleining, 2017 ; Silva et al., 2017 ; Ahmed et al., 2018 ). Therefore, gallic acid has been recognized as an inducer of apoptosis in cancer cell lines.…”