Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

Abstract

Despite the fact that various studies have investigated the clinical relevance of ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy, little has been reported regarding the efficient strategy for improving its oral bioavailability. In this study, we report the formulation of EA-loaded nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as bioavailability after oral administration. Poly(ε-caprolactone) (PCL) was selected as the biodegradable polymer for the formulation of EA-NPs through the emulsion–diffusion–evaporation technique. The obtained NPs have been characterized by measuring particle size, zeta potential, Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction. The entrapment efficiency and the release profile of EA was also determined. In vitro cellular uptake and cytotoxicity of the obtained NPs were evaluated using Caco-2 and HCT-116 cell lines, respectively. Moreover, in vivo study has been performed to measure the oral bioavailability of EA-NPs compared to free EA, using New Zealand white rabbits. NPs with distinct shape were obtained with high entrapment and loading efficiencies. Diffusion-driven release profile of EA from the prepared NPs was determined. EA-NP-treated HCT-116 cells showed relatively lower cell viability compared to free EA-treated cells. Fluorometric imaging revealed the cellular uptake and efficient localization of EA-NPs in the nuclear region of Caco-2 cells. In vivo testing revealed that the oral administration of EA-NPs produced a 3.6 times increase in the area under the curve compared to that of EA. From these results, it can be concluded that incorporation of EA into PCL as NPs enhances its oral bioavailability and activity.

Antioxidants in Cancer Therapy: Recent Trends in Application of Nanotechnology for Enhanced Delivery

“…In a study by Mady and Shaker on the preparation of ellagic acid-polymeric nanoparticles using the emulsion-diffusion-evaporation method, the results showed that they were able to sustain the diffusion release of ellagic acid and enhance its cytotoxicity (6.9-fold) against the colon adenocarcinoma, thus improved ellagic acid bioavailability and its anticancer efficacy [32]. Rocha et al also proved the efficacy of using polymeric nanoparticles in delivery of catechin for prostate cancer treatment [33].…”

Encapsulation of ellagic acid from pomegranate peels in microalgae optimized by response surface methodology and an investigation of its controlled released under simulated gastrointestinal studies

“…Found in many fruits (especially pomegranates, raspberries, blueberries, strawberries, walnuts, and grapes) (Hajipour et al., 2018), ellagic acid (EA) is a type of antioxidant that is naturally occurring and widely used for cancer treatment (Verotta et al., 2018). Recent studies have described EA as a naturally occurring bioactive polyphenolic substance (Mady & Shaker, 2017). In addition to its advantages, the disadvantages of EA include poor solubility (9.7 µg/mL) in water at pH 7.4, poor permeability and poor stability at physiological pH for hepatic metabolisms (Madrigal‐Carballo et al., 2010).…”

Antiinflammatory and anti‐cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies

“…All these studies revealed that these modifications improve the anticancer effects of EA. In another study, Mady et al found that the encapsulation of EA nanoparticles in Poly ε‐caprolactone (PCL) increases the oral bioavailability and activity of EA (Mady & Shaker, ). However, in our knowledge, there is no well‐known method to increase the bioavailability of EA and further investigations seem to be necessary.…”