Arterial Pharmacokinetics of Red Wine Polyphenols: Implications for Novel Endovascular Therapies Targeting Restenosis

Kleinedler, James J.; Pjescic, Ilija; Bullock, Kirby K.; Khaliq, Abdul; Foley, John D.; Dugas, Tammy R.

doi:10.1002/jps.23074

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…Our pNP drug entrapment system releasing the drugs only very slowly over 10 days should also protect against systemic release of polyphenols prior to arrival at the blockage. As we've shown previously, the therapeutic indices for resveratrol and quercetin are far greater than that of paclitaxel, 9 presumably making their systemic toxicity upon release in the blood much less of a risk.…”

Section: Introductionmentioning

confidence: 76%

“…more favorable therapeutic indices, reducing inflammatory cell activation and vascular smooth muscle cell proliferation without inducing overt cellular toxicity. 9,12 As demonstrated by Panyam and Labhasetwar, 15 The nanoparticles synthesized and tested proved to be biocompatible with minimal cytotoxicity, met parameters ideal for cellular uptake and provide an extended period of release. Note that release for ≥ 10 days, as was demonstrated here, is ideal for these devices, because the cellular events promoting restenosis typically occur…”

Section: Biocompatibilitymentioning

confidence: 85%

“…We've shown that the red wine polyphenols resveratrol and quercetin are less toxic to vascular cells, 9 demonstrating a higher therapeutic index compared to paclitaxel, 9 and promote re-endothelialization. 8,10 We thus propose that DCB achieving sustained release of these polyphenols are a desirable solution for PAD interventions.…”

Section: Introductionmentioning

confidence: 99%

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Nanoentrapped polyphenol coating for sustained drug release from a balloon catheter

et al. 2018

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Peripheral artery disease is a cardiovascular disease characterized by a narrowing of arteries that supply blood to the extremities, particularly, the legs. When surgical intervention is warranted, the primary approach is balloon angioplasty. Drug coated balloons (DCB) designed to release antimitogenic agents to the site of the blockage are a relatively new product aimed at reducing artery re-narrowing, or restenosis, after intervention. However, first generation DCB utilize mainly direct application of the chemotherapy drug paclitaxel, along with hydrophilic excipients to facilitate uptake into the tissue, and the majority of drug is released from the DCB systemically. We thus designed a drug-eluting nanoparticle delivery system for firm attachment to the balloon surface and only slow release of its entrapped drugs within a fluid environment. We furthermore chose the relatively nontoxic polyphenols resveratrol and quercetin as active agents we've shown reduce smooth muscle cell proliferation and inflammatory cell and platelet activation, all contributing events in restenosis. A polymeric nanoparticle (pNP) system based on poly(lactic-co-glycolic) acid but possessing a positive charge was designed for firm attachment to the balloon matrix, followed by adhesion to the negatively charged bilayer of the vascular wall. As a first step toward testing its biologic properties, drug elution into a simulated blood fluid was determined, as well as the fold enrichment of cells with drug after exposure to the drug-entrapped pNPs compared to drugs only. Cytotoxicity to vascular smooth muscle cells was assessed, along with their biocompatibility, determined as their ability to promote red blood cell lysis. The drug-entrapped pNP system showed excellent biocompatibility with limited cytotoxicity. In addition, the pNPs released the two drugs only very slowly over 10 days. Development of a spray process for delivering the drug-entrapped pNPs to a balloon surface and in vivo testing in small animals appears warranted. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018.

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Section: Introductionmentioning

confidence: 76%

Section: Biocompatibilitymentioning

confidence: 85%

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Nanoentrapped polyphenol coating for sustained drug release from a balloon catheter

et al. 2018

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“…In addition, hydrolysis mechanisms would enhance the accumulation in juices of individual phenolic compounds, mainly glucosides, galactosides, and aglycones along with some rutinosides and other glycosidic combinations linked to the flavonol nucleus, that could be better absorbed in the small intestine and reach the bloodstream . Several works have reported the pharmaceutical usefulness of grape and wine phytochemicals. − Nevertheless, further studies are needed to legitimize grape extracts as useful dietary supplements. Therefore, investigation of their radical-scavenging properties is of interest, primarily to discover promising new sources of natural antioxidants, functional foods, food supplements, and nutraceuticals.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Profile and in Vitro Cardiac Radical-Scavenging versus Pro-oxidant Effects of Commercial Red Grape Juices (Vitis vinifera L. cv. Aglianico N.)

Tenore

Manfra

Stiuso

et al. 2012

J. Agric. Food Chem.

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Several works have reported on the pharmaceutical usefulness of grape phytochemicals. Nevertheless, the scientific literature needs further studies to consider grape extracts as useful dietary supplements. The aim of the present work was to hypothesize for the first time the use of whole commercial red grape juices as food supplements potentially useful against both physiological and induced cardiac oxidative stress. First of all, the results indicated a good antioxidant stability of the juice sample to lyophilization that may be reasonably regarded as a suitable process for the formulation of food supplements. Then, the processed sample (lioRGJ) was tested on cardiac-derived H9C2 myocytes to ascertain its effects on reactive oxygen species (ROS) generation and caspase-3 activity incubating cardiomyocytes with lioRGJ at increasing doses (0.01-1 μg). Experiments showed an appreciable direct radical-scavenging activity at a maximum sample dose of 0.01 μg that made the caspase-3 activity decrease by about 47% (P < 0.001). Cardiac cells were exposed to 1 μM doxorubicin and its combination with different doses of lioRGJ. A maximum sample aliquot of 0.01 μg seemed to effectively contrast the induced oxidant injury, decreasing the ROS levels by about 31% and depressing the caspase-3 activity by about 60% (P < 0.001). In both assays, pro-oxidant effects at higher sample concentrations were detected as indicated by the increase in both ROS generation and apoptotic activity. The data suggested the possible employment of the juice sample as a food supplement with prospective cardioprotective benefits, although further studies are needed to optimize its dosages to avoid harmful pro-oxidant effects.

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“…In addition, a human study has shown dose dependent increases in cerebral blood flow from resveratrol at 5.65 and 14.4 ng/mL (0.025 and 0.061 µM) [28]. This data is supportive of the pharmacology of the aforementioned resveratrol stent [105], and novel dosage forms from the activation of eNOS and upstream effectors relating to cardiovascular disease [88,106].…”

Section: Limitations Of Current Resveratrol Bioavailability Researchmentioning

confidence: 87%

Enhancing the Delivery of Resveratrol in Humans: If Low Bioavailability is the Problem, What is the Solution?

Smoliga

Blanchard²

2014

Molecules

181

144

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Abstract:Resveratrol has emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. The poor bioavailability of resveratrol in humans has been a major concern for translating basic science findings into clinical utility. Although a number of positive findings have emerged from human clinical trials, there remain many conflicting results, which may partially be attributed to the dosing protocols used. A number of theoretical solutions have been developed to improve the bioavailability of resveratrol, including consumption with various foods, micronized powders, combining it with additional phytochemicals, controlled release devices, and nanotechnological formulations. While laboratory models indicate these approaches all have potential to improve bioavailability of resveratrol and optimize its clinical utility, there is surprisingly very little data regarding the bioavailability of resveratrol in humans. If bioavailability is indeed a limitation in the clinical utility of resveratrol, there is a need to further explore methods to optimize bioavailability in humans. This review summarizes the current bioavailability data, focusing on data from humans, and provides suggested directions for future research in this realm.

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Arterial Pharmacokinetics of Red Wine Polyphenols: Implications for Novel Endovascular Therapies Targeting Restenosis

Cited by 6 publications

References 41 publications

Nanoentrapped polyphenol coating for sustained drug release from a balloon catheter

Nanoentrapped polyphenol coating for sustained drug release from a balloon catheter

Antioxidant Profile and in Vitro Cardiac Radical-Scavenging versus Pro-oxidant Effects of Commercial Red Grape Juices (Vitis vinifera L. cv. Aglianico N.)

Enhancing the Delivery of Resveratrol in Humans: If Low Bioavailability is the Problem, What is the Solution?

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