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

Authors Mady FM, Shaker MA

Received 30 July 2017

Accepted for publication 9 September 2017

Published 10 October 2017 Volume 2017:12 Pages 7405—7417

DOI https://doi.org/10.2147/IJN.S147740

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lakshmi Kiran Chelluri

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster


Fatma M Mady,1,2 Mohamed A Shaker1,3

1Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Al Madina Al Munawara, Saudi Arabia; 2Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia, 3Pharmaceutics Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt


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.

Keywords: nanoparticles, ellagic acid, poly(ε-caprolactone), bioavailability, cytotoxicity, oral administration

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