Cherries are known for their nutraceutical properties, in particular for their antioxidant ability due to their polyphenol content, which causes a reduction of cardiovascular disease (CVD) risk factors. However, once ingested these molecules are degraded in the Gastrointestinal (GI) tract before reaching the blood, which is the action site. The object of the present work is to evaluate the ability of cherry extract (CE), encapsulated in nanoparticles (NPs) based on different chitosan (Ch) derivatives, to promote a protective effect of human umbilical vein endothelial cells (HUVECs) involved in vascular dysfunction against oxidative stress. CE-loaded NPs based on quaternary ammonium chitosan (NP1) and an S-protected thiolated derivative thereof (NP2) were prepared. The mean particle size (NP1 344.9 ± 17.8, NP2 339.9 ± 68.2 nm), the polydispersity index, the encapsulation efficiency (NP1 78.4 ± 4.5, NP2 79.8 ± 0.6%), and the zeta potential (NP1 14.8 ± 0.3, NP2 15.8 ± 0.5 mV) did not appear to be significantly different. Both NP types improved the CE apparent permeation parameters with respect to the control. Conversely, CE-loaded NP2 protected HUVECs from oxidative stress and reduced reactive oxygen species (ROS) production more than CE-loaded NP1 and free CE. In addition to promoting HUVEC resistance, NP2 could be a useful tool to overcome the problem of cherry seasonality.

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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.