title: Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.
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.
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA ; Cancer Research Center, University at Albany, Rensselaer, NY, USA.
authors.forename: Amit B
authors.initials: AB
authors.lastname: Shirode
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Dhruba J
authors.initials: DJ
authors.lastname: Bharali
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA ; Cancer Research Center, University at Albany, Rensselaer, NY, USA.
authors.forename: Sameera
authors.initials: S
authors.lastname: Nallanthighal
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA ; Cancer Research Center, University at Albany, Rensselaer, NY, USA.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Coon
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA ; Cancer Research Center, University at Albany, Rensselaer, NY, USA.
authors.forename: Ramune
authors.initials: R
authors.lastname: Reliene
mesh_terms: D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D029561:Lythraceae / Q000737:chemistry*; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D053769:Nanocapsules; D010936:Plant Extracts
keywords: Hs578T cells; MCF-7 cells; PLGA–PEG nanoparticles; ellagic acid; pomegranate extract; punicalagin