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Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress: Mucoadhesive Chitosan vs. Poly(lactic-co-glycolic acid) Nanoparticles

1
Department of Life Sciences, University of Siena, via P.A. Mattioli 4, 53100 Siena, Italy
2
Department of Pharmacy, University of Pisa, via Bonanno 33, 56100 Pisa, Italy
3
Cardiovascular Research Laboratory, Department of Surgery, Medical, Molecular, and Critical Area Pathology, University of Pisa, via Paradisa 2, 56100 Pisa, Italy
4
Interdepartmental Research Center Nutraceuticals and Food for Health, University of Pisa, via Borghetto 80, 56100 Pisa, Italy
5
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen 208, 4200-153 Porto, Portugal
6
INEB—Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
7
ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
8
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1759; https://doi.org/10.3390/ijms20071759
Received: 12 March 2019 / Revised: 1 April 2019 / Accepted: 8 April 2019 / Published: 10 April 2019
(This article belongs to the Special Issue Chitosan-Based Nanoparticles)
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Abstract

Polyphenolic compounds contained in cherry extract (CE) are well known for their antioxidant and anti-inflammatory properties. Unfortunately, most of these natural compounds have low oral bioavailability, reducing their widespread use. Here, different concentrations of polyphenol-rich CE from Tuscany (Italy), encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), were compared with those encapsulated in two NP types, different from each other in terms of mucoadhesivity, obtained with chitosan derivatives (Ch-der), regarding CE gastrointestinal (GI) permeability and protective effect on oxidative stress. Different NP systems were physico-chemically characterized, and the antioxidant GI permeability was evaluated in a triple-cell co-culture model (Caco-2/HT29-MTX/Raji B), resembling the intestine. PLGA NPs efficiently entrapped CE (up to 840 µg gallic acid equivalent (GAE)/mL) without altering size (210 nm), polydispersity index (0.05), or zeta potential (−10.7 mV). Such NPs promoted permeation of encapsulated CE at a CE polyphenolic concentration of at least 2 µg GAE/mL. More mucoadhesive NPs from Ch-der, coded quaternary ammonium S-protected thiolated chitosan (QA-Ch-S-pro) NP, promoted CE GI permeation of 0.5 µg GAE/mL. At higher concentrations of Ch-der polymers, the resulting NPs containing CE were toxic toward Caco-2 and HT29-MTX cells. CE protected human umbilical vein endothelial cells (HUVECs) from oxidative stress and maintained its activity when entrapped in PLGA NPs. CE encapsulated in QA-Ch-S-pro NP protected HUVECs from oxidative stress, even more effectively than non-encapsulated CE. Furthermore, mucoadhesive NPs from Ch-der were more effective antioxidant protectors than PLGA NPs, but less cytotoxic PLGA NPs could be more useful when comparatively high therapeutic antioxidant doses are needed. View Full-Text
Keywords: sweet cherry (Prunus avium L.); polyphenols; chitosan nanoparticles; PLGA nanoparticles; intestinal permeability; oxidative stress; HUVECs sweet cherry (Prunus avium L.); polyphenols; chitosan nanoparticles; PLGA nanoparticles; intestinal permeability; oxidative stress; HUVECs
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Beconcini, D.; Fabiano, A.; Di Stefano, R.; Macedo, M.H.; Felice, F.; Zambito, Y.; Sarmento, B. Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress: Mucoadhesive Chitosan vs. Poly(lactic-co-glycolic acid) Nanoparticles. Int. J. Mol. Sci. 2019, 20, 1759.

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