Stability Of Resveratrol Research Articles

Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology.

Resveratrol (RSV) is well known for its anti-oxidant and anti-aging properties. However, resveratrol is insoluble in water and has stability issues. Recently, efforts were placed to prepare a resveratrol-based advanced anti-aging topical product but it contains harsh organic solvents and oils that could be harmful to the human body and the environment. Hence, we propose the use of a multifunctional dendrimer to solve the solubility and stability issues of resveratrol. A dendrimer-resveratrol complex was prepared, optimized and tested for solubility enhancement, stability in solution and cream dosage forms. We have also developed a high performance liquid chromatography method to measure the resveratrol within the final product. PAMAM dendrimers increased the solubility and stability of resveratrol in water and semisolid dosage forms. Therefore, this product would be water based ‘green’ formulation devoid of harsh organic solvents and oils and can be safely applied to the skin. Additionally, we have shown that the dendrimer helped to increase overall RSV loading and skin penetration of resveratrol. The dendrimer-RSV formulation was successfully scaled up towards commercialization. Dendrimer with RSV has led to an innovation in anti-aging cream and solutions that could be commercially marketed. Dendrimer-RSV complex could also be added to other product forms for additional purposes and applications.

Synthesis and Characterization of Novel Copolymeric Resveratrol Conjugates

Resveratrol (RSV), naturally found in plants, is known to have health benefits and has been proposed as a potential anticancer and cardioprotective drug. However, due to its molecular structure, it undergoes rapid metabolism in the body resulting in low bioavailability. Novel polymeric methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) RSV conjugates with varying PCL chain lengths have been synthesised and formulated into micelles and/or nanoparticles for preliminaryin vitrostability studies. RSV conjugated with mPEG2000-PCL9500 was found to have improved solubility and stability of RSV as compared to RSV alone. The length of the PCL chain was found to affect the micelle formation, hence the stability in physiological buffers and rat plasma.

Pomegranate Seed Oil Exerts Synergistic Effects with trans-Resveratrol in a Self-nanoemulsifying Drug Delivery System.

Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.

Pre-formulation studies of resveratrol

Context: Resveratrol, a natural compound found in grapes, has potential chemotherapy effects but very low oral bioavailability in humans.Objective: To evaluate the solubility, pH stability profile, plasma protein binding (PPB) and stability in plasma for resveratrol.Methods: Solubility of resveratrol was measured in 10 common solvents at 25 °C using HPLC. The solution state pH stability of resveratrol was assessed in various United States Pharmacopeia buffers ranging from pH 2 to 10 for 24 h at 37 °C. Samples were analyzed up to 24 h. Human PPB was determined using ultracentrifugation technique. Standard solutions of drug were spiked to blank human plasma to yield final concentrations of 5, 12.5 or 25 μg/mL for determination. Finally, stability of resveratrol in human and rat plasma was also assessed at 37 °C. Aliquots of blank plasma were spiked with a standard drug concentration to yield final plasma concentration of 50 μg/mL. Samples were analyzed for resveratrol concentration up to 96 h.Results: Resveratrol has wide solubility ranging from 0.05 mg/mL in water to 374 mg/mL in polyethylene glycol 400 (PEG-400). Resveratrol is relatively stable above pH 6 and has maximum degradation at pH 9. The mean PPB of resveratrol is 98.3%. Resveratrol degrades in human and rat plasma in a first-order process with mean half lives of 54 and 25 h, respectively.Conclusion: Resveratrol is more soluble in alcohol and PEG-400 and stable in acidic pH. It binds highly to plasma proteins and degrades slower in human then rat plasma.

Effect of chitosan concentration on PLGA microcapsules for controlled release and stability of resveratrol

The polyphenols as nutraceutical and therapeutic agents are gaining growing interest for their beneficial effects and potential in human health. In order to protect their scaffolds and functionality, and to improve the bioavailability, the microencapsulation can represent a promising strategy.This study reports on the formulation of the natural resveratrol (RSV) into microcapsules (MCs) prepared by using different concentrations of chitosan (CS) and poly(D,L-lactic-co-glycolic acid) (PLGA) as polymeric matrix. MCs were prepared by W/O/W double emulsion method and characterized in terms of morphology, size, encapsulation efficiency, physicochemical and thermal properties. RSV release behavior from MCs was evaluated under simulated gastrointestinal fluids, and the long term stability was monitored at different storage conditions.MCs resulted to have spherical shape and different morphology, with size ranging from 11 to 20μm, and encapsulation efficiencies of 40–52%, depending on the CS concentration. Moreover, MCs containing CS exhibited a significant lower release of RSV than those containing only PLGA. Furthermore, all tested formulations were able to ensure a good retention and stability of encapsulated RSV until 6 months.In summary, CS/PLGA MCs can be proposed as an attractive delivery system to control the release and long term protection of RSV.

Chemistry, Stability and Bioavailability of Resveratrol

Resveratrol is a bioactive polyphenol found in many vegetables. It is well known for its multiple pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, anticancer, neuroprotective and cardioprotective effects. In vitro evidence of resveratrol efficacy is widespread, however, many concerns regarding its effectiveness in vivo arise from its poor stability in vitro and bioavailability following oral ingestion. This review focuses on the in vitro stability, with special focus on the photochemical stability of resveratrol, and on the therapeutic perspectives of this molecule due to its low bioavailability.

Improved Stability of trans-Resveratrol in Aqueous Solutions by Carboxymethylated (1,3/1,6)-β-d-Glucan

Resveratrol is a polyphenolic compound endowed with multiple health benefits. However, its limited bioavailability and poor stability in solution hamper its use in pharmaceutical applications. Due to its low solubility in water, solvents such as ethanol and dimethyl sulfoxide are often used to dissolve resveratrol. However, these solvents have adverse effects on cultured cells or in vivo. The purpose of this study was to develop an aqueous liquid formulation of resveratrol in combination with a modified glucan, the carboxymethylated (1,3/1,6)-β-D-glucan (CM-glucan). The proposed liquid formulation conferred stability to resveratrol without affecting its antioxidant capability. Shelf-life measurements revealed that resveratrol in aqueous solution is degraded within a few weeks, due to spontaneous oxidation. In contrast, the combination with CM-glucan matrix exerted a strong stabilizing effect in aqueous medium and increased resveratrol stability up to 12 months at 25 °C. These data provide evidence of a stable resveratrol formulation in liquid suspensions and support the possible development of pharmaceutical applications of this association in biopharmaceutics and drug delivery.

Thermal transitions of resveratrol on a carbon black surface

Methods of thermogravimetric analysis, differential scanning calorimetry, and thermal desorption mass-spectrometry are used to study the processes of thermolysis of resveratrol on the surface of graphitized thermal carbon black (GTCB). The results obtained in thermolysis of pure resveratrol and resveratrol adsorbed on GTCB from diethyl ether are compared. The regions of maximum evolution of thermolysis products are determined; their compositions are identified; an increase in thermal stability of resveratrol supported on the surface of graphitized thermal carbon black is observed.

Biological Relevance of the Interaction Between Resveratrol and Insulin

In view of synergistic effect of resveratrol and insulin in the prevention and treatment of many chronic diseases, the interaction between them was studied and its biological implication was further discussed. Insulin could interact with resveratrol to form 1:1 complex with the binding constant of 1.03 × 103 M−1 at 298 K. The binding was spontaneous and insulin/resveratrol complex formation was an exothermal reaction. Hydrogen bond and van der Waals force played key roles in the binding process. Kinetic study indicates that resveratrol binding to insulin conformed to the first-order exponential decay function. The interaction decreased the polarity around tyrosine residue and α-helical content, destroyed the disulfide bridges, depolymerized insulin dimers to monomer, and altered the orientation of aromatic side chains in the insulin. Additionally, insulin increased resveratrol stability. These results well confirm synergistic effect of resveratrol and insulin in vitro. It would give a deeper insight into resveratrol as a kind of food functional factor.

Resveratrol loaded liposomes produced by different techniques

Abstract Several different methods for production of liposomes incorporating resveratrol were investigated and compared from the aspect of size distribution, surface charge, entrapment efficiency, phase behavior and stability. Thin film method and proliposome method provided high entrapment efficiency (92.9% and 97.4%, respectively). Extrusion and sonication techniques were applied to obtain particles of the average diameter between 120 and 270 nm. The sonicated liposomes incorporated resveratrol (44–56%) fewer than extruded vesicles (92–96%). Antioxidative activity of resveratrol was retained upon encapsulation. Differential scanning calorimetry was performed in order to study the interaction of liposomal membranes with resveratrol, and their physical state. The release studies performed in Franz diffusion cell showed that liposomes impart slow diffusion of resveratrol, where diffusion resistance derived from liposomal membrane ranged from 5.90 ∙ 10 5 to 9.55 ∙ 10 5 s/m depending on the size of particles. Cytotoxicity of the formulations was evaluated via morphological changes of keratinocytes treated by liposomes. Industrial Relevance Resveratrol displays many health-beneficial properties and possesses a remarkably strong antioxidant activity. Although often consumed in food, the positive effects of resveratrol are restricted because it is prone to oxidation, poorly absorbed when orally administrated, and cytotoxic in higher total dosages (though relatively high local concentrations are required for an effect). Encapsulation is one way to improve bioavailability and stability of resveratrol; herein the main challenge is to find a suitable solution, as resveratrol is weakly water soluble. This has motivated us to design new formulations based on liposomes for delivering of resveratrol. In the food sector, liposomes have been investigated for delivering proteins, enzymes, antioxidants, flavors and vitamins. The mean advantage of liposomes over other encapsulation technologies (spray-drying, extrusion, and fluidized beds) is the stability that liposomes impart to water-soluble compounds in aqueous surroundings. Liposomes are able to stabilize the encapsulated materials against a range of environmental and chemical changes. Another important characteristic of liposomes is that, unlike many other existing encapsulants, they can be utilized in the entrapment, delivery, and release of poorly water soluble compounds, such as resveratrol, and they are also convenient for water-soluble, lipid-soluble, and amphiphilic compounds. As liposomes could be produced from naturally occurring components, regulatory issues that may prevent the application in food systems are potentially diminished, and new formulations could be quickly implemented. Despite benefits described here, up to date little use of liposomes in food systems has been made, as current manufacturing processes are mainly time consuming, often consisting of several steps with high costs of raw materials. Another problem is that devices available commercially which are utilized for production of liposomes are able to process only small quantities. Therefore, our research is devoted to the development of the process for liposome production which is easy to scale up, and at the same time, is effective as the common way based on thin film hydration process. The process elaborated in our study utilizes a commercial lipid mixture. The method used called proliposome method is based on replacement of ethanol solvent by aqueous media. For liposome downsizing, sonication (which can be easily modified to increase sample volume capability) is tested versus membrane extrusion (equipment for small–large batches is readily available). The goal of this article is to provide evidence for food manufacturers and food scientists to make broader use of resveratrol-loaded liposomes that can add value and improve the quality of existing food products.

Resveratrol Binding to Fibrinogen and its Biological Implication

In light of important implication of fibrinogen and resveratrol in the platelet aggregation and thrombus formation, the interaction between them was studied, and its biological implication was further explained. Fibrinogen could interact with resveratrol to form 1:1 complex with the binding constant of 1.11 × 104 M−1. The binding was spontaneous and fibrinogen/resveratrol complex formation was an exothermal reaction. Electronic interaction and hydrogen bonding played key roles and non-radiation energy transferred from fibrinogen to resveratrol in the binding process. Kinetic study indicated that resveratrol linearly combined to fibrinogen along with the prolonged time. The addition of resveratrol changed fibrinogen conformation including its second structure resulting in increase of polarity around tyrophore residue and decrease of α-helical structure in the protein. Additionally, fibrinogen obviously increased resveratrol stability. It would give a deeper insight into resveratrol as a kind of functional factor.

Resveratrol-Containing Gel for the Treatment of Acne Vulgaris

Acne vulgaris is a complex, chronic, and common skin disorder of pilosebaceous units. The major pathogenic factors involved are ductal hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The aim of the study was to investigate the therapeutic effects of resveratrol, a natural phytoalexin produced by some spermatophytes, such as grapes and other plants, on acneic skin. Resveratrol was incorporated in a carboxymethylcellulose-based gel. The chemical stability of resveratrol after storage at 4°C for 30 days was investigated by high-performance liquid chromatography (HPLC). The resveratrol-containing hydrogel was administered to 20 patients affected by acne vulgaris enrolled in this single-blind study. The resveratrol-containing formulation was applied daily as a solo treatment on the right side of the face for 60 days, while the hydrogel vehicle was applied to the left side of the face as a control. To objectively evaluate the results, a digital photographic database was used to collect images. The number and type of lesions were recorded for each patient, to compare the Global Acne Grading System (GAGS) score before treatment with that obtained at the end of the study. Moreover, with the innovative technique of follicular biopsy, areas of acneic skin were prepared for histopathology. The average area occupied by microcomedones at baseline was compared with that at the end of treatment. HPLC analysis demonstrated that resveratrol, upon incorporation into the gel, did not convert to its cis-isomer when stored at 4°C for 30 days. All patients were satisfied with the active treatment and none experienced adverse effects. Clinical evaluation showed a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel. This pilot study showed positive results for resveratrol gel in acne, and should be considered a valid starting point for further testing of the effectiveness of this molecule in different concentrations and formulations and in a larger group of patients.

Cyclodextrin-Based Nanosponges for Delivery of Resveratrol: In Vitro Characterisation, Stability, Cytotoxicity and Permeation Study

The aim of this work was to increase the solubility, stability and permeation of resveratrol by complexation with cyclodextrin-based nanosponges (NS). Nanosponges are recently developed hyper-cross-linked cyclodextrin polymers nanostructured to form three-dimensional networks; they are obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole. They have been used to increase the solubility and stability of poorly soluble actives. This study aimed at formulating complexes of resveratrol with β-cyclodextrin nanosponges in different weight ratios. DSC, FTIR and X-ray powder diffraction (XRPD) studies confirmed the interaction of resveratrol with NS. XRPD showed that the crystallinity of resveratrol decrease after encapsulation. The particle sizes of resveratrol-loaded NS are in between 400 to 500 nm with low polydispersity indices. Zeta potential is sufficiently high to obtain a stable colloidal nanosuspension. TEM measurement also revealed a particle size around 400 nm for NS complexes. The in vitro release and stability of resveratrol complex were increased compared with plain drug. Cytotoxic studies on HCPC-I cell showed that resveratrol formulations were more cytotoxic than plain resveratrol. The permeation study indicates that the resveratrol NS formulation showed good permeation in pigskin. The accumulation study in rabbit mucosa showed better accumulation of resveratrol NS formulation than plain drug. These results signify that resveratrol NS formulation can be used for buccal delivery and topical application.

Transport, stability, and biological activity of resveratrol

Numerous studies have reported interesting properties of trans-resveratrol, a phytoalexin, as a preventive agent of several important pathologies: vascular diseases, cancers, viral infections, and neurodegenerative processes. These beneficial effects of resveratrol have been supported by observations at the cellular and molecular levels in both cellular and in vivo models, but the cellular fate of resveratrol remains unclear. We suggest here that resveratrol uptake, metabolism, and stability of the parent molecule could influence the biological effects of resveratrol. It appears that resveratrol stability involves redox reactions and biotransformation that influence its antioxidant properties. Resveratrol's pharmacokinetics and metabolism represent other important issues, notably, the putative effects of its metabolites on pathology models. For example, some metabolites, mainly sulfate-conjugated resveratrol, show biological effects in cellular models. The modifications of resveratrol stability, chemical structure, and metabolism could change its cellular and molecular targets and could be crucial for improving or decreasing its chemopreventive properties.

Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet

Recently resveratrol, a compound naturally occurring in various plants, has been proposed as a potential anti-obesity compound. The aim of the present work was to analyse the effects of different doses of resveratrol on body fat and serum parameters in rats. Thirty-two male Sprague-Dawley rats were randomly divided into four groups and fed on a hypercaloric diet for 6 weeks. The doses oftrans-resveratrol used were 6, 30 and 60 mg/kg body weight/d in RSV1, RSV2 and RSV3 groups respectively. The stability of resveratrol when added to the diet was evaluated. Blood samples were collected, and white adipose tissue from different anatomical locations, interscapular brown adipose tissue, gastrocnemious muscles and liver were weighed. Commercial kits were used to measure serum cholesterol, glucose, triacylglycerols and non-esterified fatty acids. While the lowest dose did not have a body fat reducing effect, the intermediate dose reduced all the white adipose depots. The highest dose significantly reduced mesenteric and subcutaneous depots but not epididymal and perirenal tissues. Although the reduction in all the anatomical locations analysed was 19% in the RSV3 group, in the RSV2 group it was 24%. No significant differences among the experimental groups were found in brown adipose tissue, gastrocnemious muscle or liver weights. Serum parameters were not affected by resveratrol intake because no differences among the experimental groups were observed. These results suggest that resveratrol is a molecule with potential anti-obesity effect. The most effective of the three experimental doses was 30 mg/kg body weight/d.

Radiation stability of resveratrol in immobilization on poly vinyl pyrrolidone hydrogel dressing for dermatological use

The polyphenol trans-resveratrol is a natural phytoalexin, which is found in red wine and in a wide variety of plant species. Resveratrol displays a wide array of biological activities, such as modulation of lipid metabolism, anti-inflammatory and antioxidant activities. This active compound immobilized in polyvinylpyrrolidone (PVP) hydrogel could be very interesting for topical administration, as a dressing form for dermatological use. However, PVP hydrogel obtained by radiation-induced crosslinking can cause undesirable hydrolysis reactions in the active compound. The aim of this work was to verify the resveratrol stability after irradiation at 0.5 and 1 kGy in the presence of ethanol, methanol or tert-butyl alcohol. The integrity of these samples was compared to unirradiated resveratrol by HPLC. The PVP hydrogel matrix was characterized by gel fraction, swelling and in vitro biocompatibility test. The results of gel fraction and swelling degree were approximately 90% and 1600%, respectively. The cytotoxicity assay showed absence of toxicity for this formulation after crosslinking and sterilization, indicating that the PVP hydrogel formulation was appropriate for resveratrol immobilization to produce a dressing for dermatological use.

Resveratrol and Its Glycon Piceid Are Stable Polyphenols

Plant extracts containing phytopolyphenols, including resveratrol, are extensively used as nutraceutical supplements. Recent reports allege their lack of stability at ambient conditions. We have studied the stability of resveratrol and its glycon piceid in a mixture with a whole grape extract for 2 years (long-term stability) under Good Manufacturing Practice pharmaceutical protocols (at 60% humidity and 25 degrees C). The neat compounds were followed for 4 years under conditions of "accelerated stability," at 75% humidity and 40 degrees C, all in the presence of ambient air. Chromatographic analysis did not detect any instability, thus disproving the claims to the opposite. No storage precautions are necessary for these nutritional supplements.

Determination of trans-Resveratrol in China Great Wall ‘‘Fazenda’’ Red Wine by Use of Micellar Electrokinetic Chromatography

Resveratrol, which occurs in two isomeric forms, trans and cis, is a phytoalexin with pharmacological activity, for example anti-cancer, anti-cardiovascular disease, and life-span increasing properties. Red wine is the main source of the compound and an easy way of including resveratrol in the human diet. In the work discussed in this paper determination of resveratrol and separation of its isomers were investigated using micellar electrokinetic chromatography. The detection wavelength, micelle concentration, and applied voltage were studied and optimized. Baseline separation of the isomers of resveratrol was achieved. The stability of resveratrol under typical consumer conditions was also evaluated. When resveratrol was determined in the top-grade dry-red wine China Great Wall ‘‘Fazenda’’ by use of our analytical method the concentration was found to be ≥1.3 ± 0.1 mg L−1.

Capillary electrophoresis determination, synthesis, and stability of resveratrol and related 3-O-beta-D-glucopyranosides.

Because of the health implications of resveratrol and piceid, which are widely present in foods, we focused our attention on the development of a highly efficient methodology for their characterization and measurement. On the basis of our experience in capillary electrophoresis for separation of polyphenolic compounds, we developed a general analytical method for piceid identification which was also applicable to complex natural mixtures such as red wine. In view of its very limited availability from natural sources, we first directed our attention to the development of a synthetic route suitable to produce an adequate amount of polydatin (piceid or resveratrol 3-O-beta-D-glucopyranoside). The latter was synthesized by a new one-step procedure which afforded the expected product in a good yield. The studied compounds were also investigated for their stability to UV irradiation.

An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine.

Resveratrol is an antioxidant found in grapes, grape products, and some other botanical sources with antiinflammatory and anticancer properties. In grapes and wine, it occurs both as free resveratrol and piceid, the 3beta-glucoside of resveratrol. Here we report a liquid chromatography-mass spectrometry method to analyze total resveratrol (including free resveratrol and resveratrol from piceid) in fruit products and wine. Samples were extracted using methanol, enzymatically hydrolyzed, and analyzed using reversed phase HPLC with positive ion atmospheric pressure chemical ionization (APCI) mass spectrometric detection. Following APCI, the abundance of protonated molecules was recorded using selected ion monitoring (SIM) of m/z 229. An external standard curve was used for quantitation, which showed a linear range of 0.52-2260 pmol of trans-resveratrol injected on-column with a correlation coefficient 0.9999. The coefficient of variance of the response factor over the same concentration range was determined to be 5.8%, and the intra-assay coefficient of variance was determined to be 4.2% (n = 7). The limit of quantitation, defined as signal-to-noise 10:1, was determined to be 0.31 pmol injected on-column. The extraction efficiency of the method was determined to be 92%. The stability of resveratrol under different conditions was also examined. For example, resveratrol was stable for up to 5 days at 4 degrees C in the dark but was not stable at room temperature without protection from light. Resveratrol was detected in grape, cranberry, and wine samples. Concentrations ranged from 1.56 to 1042 nmol/g in Concord grape products, and from 8.63 to 24.84 micromol/L in Italian red wine. The concentrations of resveratrol were silmilar in cranberry and grape juice at 1.07 and 1.56 nmol/g, respectively.