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Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention

Authors Shirode AB, Bharali DJ, Nallanthighal S, Coon JK, Mousa SA, Reliene R

Received 29 March 2014

Accepted for publication 14 September 2014

Published 9 January 2015 Volume 2015:10(1) Pages 475—484

DOI https://doi.org/10.2147/IJN.S65145

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Carlos Rinaldi

Amit B Shirode,1,2,* Dhruba J Bharali,3,* Sameera Nallanthighal,1,2 Justin K Coon,1,2 Shaker A Mousa,3 Ramune Reliene1,2

1Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA; 2Cancer Research Center, University at Albany, Rensselaer, NY, USA; 3Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA

*These authors contributed equally to this work


Abstract: Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) NPs loaded with pomegranate extract (PE) or individual polyphenols such as PU or EA. Monodispersed, spherical 150–200 nm average diameter NPs were prepared by the double emulsion–solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA–PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer.

Keywords: PLGA–PEG nanoparticles, pomegranate extract, punicalagin, ellagic acid, MCF-7 cells, Hs578T cells

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