Resveratrol nanoformulation for cancer prevention and therapy.
01 Aug 2015-Annals of the New York Academy of Sciences (Ann N Y Acad Sci)-Vol. 1348, Iss: 1, pp 20-31
TL;DR: This review focuses on the recent developments of novel nanoformulations used to deliver sustained levels of resveratrol, an extremely photosensitive compound with low chemical stability and limited bioavailibility, which limit the therapeutic application of its beneficial effects.
Abstract: Chemoprevention of human cancer(s) is a viable option for cancer control, especially when chemopreventive intervention is involved during the early stages of the carcinogenesis process. Naturally occurring bioactive food components, such as dietary polyphenols, have shown good antioxidant activity and other beneficial activities. In addition, compounds belonging to the polyphenolic chemical class may play promising roles in cancer prevention. Among them, the phytoalexin resveratrol has demonstrated antiproliferative effects, as well as the ability to inhibit initiation and promotion of induced cancer progression in a wide variety of tumor models. However, resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability and limited bioavailibility, which limit the therapeutic application of its beneficial effects. In this context, the development of innovative formulation strategies able to overcome physicochemical and pharmacokinetic limitations of this compound could be beneficial. This may be achieved via nanotechnology approaches utilizing suitable carriers that allow slow, sustained, and controlled release of the encapsulated agent. This review focuses on the recent developments of novel nanoformulations used to deliver sustained levels of resveratrol.
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TL;DR: One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells, resulting in lowering of the required therapeutic dose and in multitargeted action.
Abstract: Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, with supercritical fluid extraction highlighted as a promising eco-friendly alternative providing exceptional separation and protection from degradation of unstable polyphenols. The protective role of polyphenols against reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and predators results in several beneficial biological activities giving rise to prophylaxis or possibly even to a cure for several prevailing human diseases, especially various cancer types. Omnipresence, specificity of the response and the absence of or low toxicity are crucial advantages of polyphenols as anticancer agents. The main problem represents their low bioavailability and rapid metabolism. One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells. Another, more practiced, solution is the use of mixtures of various polyphenols that bring synergistic effects, resulting in lowering of the required therapeutic dose and in multitargeted action. The combination of polyphenols with existing drugs and therapies also shows promising results and significantly reduces their toxicity.
638 citations
Cites background from "Resveratrol nanoformulation for can..."
...Resveratrol, pterostilbene and piceatannol represent the most important constituents of stilbene class and belong to phytoalexins since they are synthesized in plants in response to fungal infection or other environmental stress [100,113,115]....
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...Like other natural polyphenols, resveratrol and piceatannol are extremely photosensitive compounds with low chemical stability and consequentially, as already mentioned, limited bioavailability, which hampers their potential for development into therapeutic agents [113,115]....
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...Although wine may be considered a predominant bioavailable dietary source of stilbenes; grapes, various berries, peanuts and available dietary supplements are all highly relevant sources as well [83,101,114,115]....
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...A wide variety of tumor models demonstrates resveratrol’s abilities to inhibit initiation and promotion of progression of several cancer types including skin, breast, prostate, colon, oral, leukemia and gastric [83,100,114,115]....
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...In particular, nanotechnological approaches could help to overcome the pharmacokinetic issues of bioactive compounds by providing improved bioavailability, overcoming the first-pass metabolism and trounce enterohepatic recirculation, by protection against degradation, enhancement in intracellular penetration and control delivery, and by reducing potential toxicity [115]....
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TL;DR: The possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, is critically discussed.
226 citations
TL;DR: It is highlighted how resveratrol, despite its unfavorable pharmacokinetics, can modulate the inflammatory pathways underlying those diseases, and it is identified future opportunities for the evaluation of its clinical feasibility.
Abstract: Inflammation is the principal response invoked by the body to address injuries. Despite inflammation constituting a crucial component of tissue repair, it is well known that unchecked or chronic inflammation becomes deleterious, leading to progressive tissue damage. Studies over the past years focused on foods rich in polyphenols with anti-inflammatory and immunomodulatory properties, since inflammation was recognized to play a central role in several diseases. In this review, we discuss the beneficial effects of resveratrol, the most widely investigated polyphenol, on cancer and neurodegenerative, respiratory, metabolic, and cardiovascular diseases. We highlight how resveratrol, despite its unfavorable pharmacokinetics, can modulate the inflammatory pathways underlying those diseases, and we identify future opportunities for the evaluation of its clinical feasibility.
167 citations
Cites background from "Resveratrol nanoformulation for can..."
...Natural products may provide one the most promising approaches for reducing cancer via chemoprevention [188]....
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TL;DR: Different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.
Abstract: Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.
121 citations
TL;DR: The results suggested that resveratrol chemosensitizes doxorubicin in combination, through inhibiting breast cancer cells proliferation and invasion, and inducing apoptosis via suppression of chronic inflammation and autophagy.
104 citations
References
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TL;DR: The arsenal of nanocarriers and molecules available for selective tumour targeting, and the challenges in cancer treatment are detailed and emphasized.
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TL;DR: The nature and contents of the various polyphenols present in food sources and the influence of agricultural practices and industrial processes are reviewed, and bioavailability appears to differ greatly between the variousPolyphenols, and the most abundantpolyphenols in the authors' diet are not necessarily those that have the best bioavailability profile.
6,842 citations
TL;DR: It is suggested that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.
Abstract: Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.
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TL;DR: PEG is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery and alternative polymers will be evaluated.
Abstract: Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.
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TL;DR: Attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
Abstract: Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis. Numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents, but attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
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