Quercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy.

BACKGROUND: Quercetin, a bioflavonoid abundant in grapefruit, onion, berries, etc., has vast therapeutic potential, especially against Type 2 diabetes and its complications. Quercetin showed similar effects as that of metformin, (widely prescribed antidiabetic drug) in cell lines models (Sajan et al., 2010; Dhanya et al., 2017). In vivo findings also showcase it as a promising agent against diabetes and its pathophysiological complications. SCOPE AND APPROACH: Quercetin can be produced on a large scale through a novel fermentation-based glycosylation strategy from cheap substrates and can be utilized as a dietary supplement. The review focuses on the mounting evidence pointing to Quercetin as a promising candidate for managing type 2 diabetes and its oxidative stress mediated pathophysiological complications. CONCLUSION: Quercetin acts on multiple targets of diabetes and regulates key signalling pathways which improve the symptoms as well as the complications of Type 2 diabetes. However further studies are needed to improve the bioavailability and to establish a dosing regimen for Quercetin.

Bioactivity, bioavailability, and gut microbiota transformations of dietary phenolic compounds: implications for COVID-19.

The outbreak of mysterious pneumonia at the end of 2019 is associated with widespread research interest worldwide. The coronavirus disease-19 (COVID-19) targets multiple organs through inflammatory, immune, and redox mechanisms, and no effective drug for its prophylaxis or treatment has been identified until now. The use of dietary bioactive compounds, such as phenolic compounds (PC), has emerged as a putative nutritional or therapeutic adjunct approach for COVID-19. In the present study, scientific data on the mechanisms underlying the bioactivity of PC and their usefulness in COVID-19 mitigation are reviewed. In addition, antioxidant, antiviral, anti-inflammatory, and immunomodulatory effects of dietary PC are studied. Moreover, the implications of digestion on the putative benefits of dietary PC against COVID-19 are presented by addressing the bioavailability and biotransformation of PC by the gut microbiota. Lastly, safety issues and possible drug interactions of PC and their implications in COVID-19 therapeutics are discussed.

Rp-HPLC Determination of Quercetin in a Novel D-α-Tocopherol Polyethylene Glycol 1000 Succinate Based SNEDDS Formulation: Pharmacokinetics in Rat Plasma.

Despite its proven efficacy in diverse metabolic disorders, quercetin (QU) for clinical use is still limited because of its low bioavailability. D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) is approved as a safe pharmaceutical adjuvant with marked antioxidant and anti-inflammatory activities. In the current study, several QU-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were investigated to improve QU bioavailability. A reversed phase high performance liquid chromatography (RP-HPLC) method was developed, for the first time, as a simple and sensitive technique for pharmacokinetic studies of QU in the presence of TPGS SNEDDS formula in rat plasma. The analyses were performed on a Xterra C18 column (4.6 × 100 mm, 5 µm) and UV detection at 280 nm. The analytes were separated by a gradient system of methanol and phosphate buffer of pH 3. The developed RP-HPLC method showed low limit of detection (LODs) of 7.65 and 22.09 ng/mL and LOQs of 23.19 and 66.96 ng/mL for QU and TPGS, respectively, which allowed their determination in real rat plasma samples. The method was linear over a wide range, (30-10,000) and (100-10,000) ng/mL for QU and TPGS, respectively. The selected SNEDDS formula, containing 50% w/w TPGS, 30% polyethylene glycol 200 (PEG 200), and 20% w/w pumpkin seed oil (PSO), showed a globule size of 320 nm and -28.6 mV zeta potential. Results of the pharmacokinetic studies showed 149.8% improvement in bioavailability of QU in SNEDDS relative to its suspension. The developed HPLC method proved to be simple and sensitive for QU and TPGS simultaneous determination in rat plasma after oral administration of the new SNEDDS formula.

Encapsulation of lipophilic polyphenols in plant-based nanoemulsions: impact of carrier oil on lipid digestion and curcumin, resveratrol and quercetin bioaccessibility.

Lipophilic polyphenol compounds (LPCs) are claimed to exhibit a broad spectrum of biological activities that may improve human health and wellbeing, including antioxidant, anti-inflammatory, and anti-cancer properties. Nanoemulsion-based delivery systems have been developed to encapsulate LPCs so as to increase their food matrix compatibility, physicochemical stability, and bioavailability. LPCs vary in their structural features, including the number and position of phenolic hydroxyl, ketone, and aliphatic groups, which results in different molecular, physicochemical, and gastrointestinal properties. In this study, we examined the impact of plant-based carrier oils (coconut, sunflower, and flaxseed oils) and LPC type (curcumin, resveratrol, and quercetin) on the in vitro gastrointestinal fate of polyphenols loaded into quillaja saponin-stabilized nanoemulsions. Coconut oil contains high levels of medium-chain saturated fatty acids (MC-SFAs), sunflower oil contains high levels of long-chain monounsaturated fatty acids (LC-MUFAs), and flaxseed oil contains high levels of long-chain polyunsaturated fatty acids (LC-PUFAs). The encapsulation efficiency and gastrointestinal stability of the LPCs were slightly lower in the MC than the LC oils. Differences in the gastrointestinal stability of the three LPCs were linked to differences in their oil-water partition coefficients. Some of the LPCs inhibited lipid digestion for certain oil types. In particular, resveratrol retarded the digestion of all three oils, but it still had the highest GIT stability and bioaccessibility. This study provides valuable information about the gastrointestinal fate of LPC-loaded nanoemulsions and highlights important differences in the behavior of LPCs with different characteristics. This knowledge may facilitate the design of more effective plant-based delivery systems for bioactive lipophilic polyphenols.

Improving gallic acid and quercetin bioavailability by polymeric nanoparticle formulation.

The anticancer activity and pharmacokinetic properties of encapsulated polyherbal nanoparticles (gallic acid (GA) and quercetin nanocomposite) and polyherbal extract (amla and pomegranate fruit peels) in normal and DMH-induced colorectal cancer in rats were examined in this work. In normal and DMH-induced rats, a pharmacokinetic study demonstrated that polyherbal nanoparticles had a typical sustained release profile with a fourfold increase in bioavailability when compared to polyherbal extract. Based on serum-concentration profiles of polyherbal nanoparticles and polyherbal extract following oral administration, the pharmacokinetic parameters for polyherbal nanoparticles and polyherbal extract were established using a single compartmental approach. This research suggests that encapsulating GA and quercetin in polymeric nanoparticles improves their oral bioavailability and anti-colon cancer efficacy. Polymeric nanoparticles could be a novel therapeutic possibility for carcinogenesis prevention.

Impact of quercetin on pharmacokinetics of quetiapine: insights from in-vivo studies in wistar rats.

Quercetin (QCN) is commonly used in high doses as a dietary supplement for weight loss. Psychotic patients are at greater risk of developing obesity than the general population. The present study was designed to understand the impact of QCN on the exposure of quetiapine (QTE), an anti-psychotic drug with narrow therapeutic index and brain penetrating capability. The content of QTE in rat plasma was analyzed through liquid chromatography-tandem mass spectrometry. The results showed a significant (p < 0.05) increase in exposure of QTE (peroral dosed) in the animals pre-treated with QCN as compared to the control group. All the animals pre-treated with QCN, succumbed to death within 3-5 min of intravenous dosing of QTE (1 mg/kg). The studies in rat liver S9 fraction indicated that QCN could increase the metabolic stability of QTE by inhibiting the activity of CYP enzymes. The brain to plasma ratio of QTE increased upon QCN pre-treatment (2.6 vs 7.7), which could be attributed to P-glycoprotein inhibition at the blood-brain barrier by QCN. The current set of studies indicated that serious herb-drug interaction between QCN and QTE might occur when they are co-administered. Caution is advised for concomitant use of QCN rich dietary supplements with QTE.

Comparative Pharmacokinetics of Gallic Acid, Protocatechuic Acid, and Quercitrin in Normal and Pyelonephritis Rats after Oral Administration of a Polygonum capitatum Extract.

Polygonum capitatum Buch.-Ham. ex D. Don is traditionally used by Hmong for the treatment of urinary tract infections and pyelonephritis. Information regarding the pharmacokinetic behavior of the extract in the condition of pyelonephritis is lacking. In the present study, we aimed to compare the pharmacokinetic properties of gallic acid (GA), protocatechuic acid (PCA), and quercitrin (QR)-the main bioactive constituents in the herb-in normal and pyelonephritis rats. The plasma samples were collected at various time points after administration of a single dose of Polygonum capitatum extract. The plasma level of GA, PCA, and QR at the designed time points was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and drug concentration versus time plots were constructed to estimate the pharmacokinetic parameters. The AUC(0-t), AUC(0-∞), MRT(0-t), and CL of GA, PCA, and QR in pyelonephritis rats was significantly different from those of the normal rats. The results indicated that the three constituents have higher rate of uptake and slower rate of elimination in the rats with pyelonephritis, suggesting altered rate and extent of drug metabolism.

Establishment of modified biopharmaceutics classification system absorption model for oral Traditional Chinese Medicine (Sanye Tablet).

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the new drugs of traditional Chinese medicine, Sanye Tablet is employed as a hypolipidemic in the traditional medicine, but the biopharmaceutical properties of the drug is still unclear. AIM OF THE STUDY: Through the study of biopharmaceutical properties, the classical biopharmaceutics classification system (BCS) can be used to classify and predict the in vivo absorption properties. On this basis, the biopharmaceutical properties closely related to traditional Chinese medicine preparations are added and a modified BCS model is established to predict and judge the absorption degree of traditional Chinese medicine compound. MATERIALS AND METHODS: Representative components of Sanye Tablet were selected and subjected to different in vitro tests. The experimental results were compared with the results of the BCS to evaluate the accuracy and applicability to Sanye Tablet. We take parameters of dissolution and stability based on product characteristics into account. A "modified-BCS" was developed and the results of the improved method and the classic method were compared. Also the ability of each classification system to predict and determine the extent of absorption of the Chinese herbal compound was investigated based on the absolute bioavailability of representative components. RESULTS: For classic BCS, the five representative components (except for nuciferine) are all class III, nuciferine is class I/II obtained by Caco-2 cell assay and class III/IV obtained by everted gut sac assay. For modified BCS, paeoniflorin is class III, rutin, hyperoside and salvianolic acid B are class III/IV, and nuciferine is class I/II based on Caco-2 cell assay, class III/IV based on everted gut sac assay. Nuciferine is the best of the five components, with absolute bioavailability reaching 61.91% based on in vivo bioavailability test. CONCLUSIONS: The five representative components (except for nuciferine) are all class III/IV, which correlates well with the absolute bioavailability results and demonstrates that they are poorly absorbed substances. The correlation between the classification results obtained using the "modified-BCS" and absorption in the body is better than the correlation obtained using the classic method, suggesting that the improved BCS is more suitable for the characterization of Sanye Tablet. These results indicate that the oral formulation of Sanye Tablet is a BCS III/IV drug.

Water-in-oil organogel based emulsions as a tool for increasing bioaccessibility and cell permeability of poorly water-soluble nutraceuticals.

The use of organogels in food and pharmaceutical sciences has several technical problems related with restricted diffusion of the drugs and lack of a proper gelator molecule. These features are important into the new product design. An alternative to improve technological properties in organogels is the use of emulsions. However, there is a lack of knowledge about the behavior on bioaccessibility and permeability of bioactives loaded into organogel-based emulsions. The objective of the present experimental work was to study the physical properties of organogel-based emulsions made with vegetable oil loaded with three different bioactives (betulin, curcumin and quercetin) and the influence on their bioaccessibility. Organogels were made of canola or coconut oils and myverol as gelator (10% w/w). Water-in-oil emulsions (at 5, 10 and 12.5 wt% of water content) were prepared by mixing the melted proper organogel and water (80 °C) under high shear conditions (20,000 rpm). Micrographs, rheological tests (amplitude, frequency, temperature sweeps and creep-compliance measurements), DSC and particle size analysis were performed to samples. In vitro digestion (oral, gastric and intestinal phase), lipolysis assays, bioaccessibility and permeability tests by cell culture of Caco-2 were made. Organogels of coconut oil have shown poor emulsification properties.

Simultaneous determination of curcumin, tetrahydrocurcumin, quercetin, and paeoniflorin by UHPLC-MS/MS in rat plasma and its application to a pharmacokinetic study.

Curcumin (CUR) is a bioactive compound present in many composite prescriptions of traditional Chinese medicine together with quercetin (QR) and paeoniflorin (PF). Little is known about the influence of QR and PF on the absorption and metabolism of CUR when the three compounds are orally co-administered. In this study, a rapid, sensitive, and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous determination of CUR, tetrahydrocurcumin (THC), QR, and PF in rat plasma by using tinidazole as the internal standard (IS). A liquid-liquid extraction method with ethyl acetate was used to pre-treat the plasma samples. Chromatographic separation was conducted on a C18 column with isocratic elution using acetonitrile and 0.1% formic acid water solution (80:20, v/v) as the mobile phase at the flow rate of 0.3 mL/min. A TSQ Quantum Access Max API mass spectrometer equipped with electrospray ionisation (ESI) source in selection reaction monitoring (SRM) mode was employed to determine transitions of m/z 369.0 → 176.9, 373.1 → 137.0, 303.0 → 228.9, 478.9 → 120.9, 248.1 → 121.0 for CUR, THC, QR, PF, and IS, respectively. The selectivity, precision, accuracy, extraction recovery, matrix effect, and stability of the method were validated. This developed and validated method was successfully applied in the pharmacokinetic study of CUR, THC, QR, and PF in rats. The effects of QR and PF on the pharmacokinetics of CUR and its metabolite, THC, were evaluated in the plasma of Sprague-Dawley rats that were orally co-administered CUR, QR, and PF. The results showed that the combined use of QR, PF, and CUR has a possible influence on the metabolism and excretion of CUR. Our work provides a fundamental method for the rapid simultaneous determination of CUR, THC, QR, and PF in rat plasma. Furthermore, this study will provide a basic method for the analysis of pharmacokinetic interaction of CUR, QR, and PF and offer a scientific basis for a possible combination therapy with the three compounds.

Application of quercetin in neurological disorders: from nutrition to nanomedicine.

Quercetin is a polyphenolic flavonoid, which is frequently found in fruits and vegetables. The antioxidant potential of quercetin has been studied from subcellular compartments, that is, mitochondria to tissue levels in the brain. The neurodegeneration process initiates alongside aging of the neurons. It appears in different parts of the brain as Aß plaques, neurofibrillary tangles, Lewy bodies, Pick bodies, and others, which leads to Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and other diseases. So far, no specific treatment has been identified for these diseases. Despite common treatments that help to prevent the development of disease, the condition of patients with progressive neurodegenerative diseases usually do not completely improve. Currently, the use of flavonoids, especially quercetin for the treatment of neurodegenerative diseases, has been expanded in animal models. It has also been used to treat animal models of neurodegenerative diseases. In addition, improvements in behavioral levels, as well as in cellular and molecular levels, decreased activity of antioxidant and apoptotic proteins, and increased levels of antiapoptotic proteins have been observed. Low bioavailability of quercetin has also led researchers to construct various quercetin-involved nanoparticles. The treatment of animal models of neurodegeneration using quercetin-involved nanoparticles has shown that improvements are observed in shorter periods and with use of lower concentrations. Indeed, intranasal administration of quercetin-involved nanoparticles, constructing superparamagnetic nanoparticles, and combinational treatment using nanoparticles such as quercetin and other drugs are suggested for future studies.

Quercetin and kaempferol increase the intestinal absorption of isorhamnetin coexisting in Elaeagnus rhamnoides (L.) A. Nelson (Elaeagnaceae) extracts via regulating multidrug resistance-associated protein 2.

BACKGROUND: Isorhamnetin (IS) is a flavonoid component with many biological activities such as antioxidant, anti-inflammatory, and anticancer, which is also the main active component in total flavones of Elaeagnus rhamnoides (L.) A. Nelson (Elaeagnaceae) (TFH); however, the interaction between IS and other components in TFH is unclear. PURPOSE: The aim of the present study was to investigate the enhancement of quercetin (QU) or kaempferol (KA) on the intestinal absorption of IS coexisting in TFH, and then preliminarily illuminate the related mechanisms. METHODS: Firstly, the intestinal absorption of IS in the presence or absence of QU or KA was conducted by in vivo pharmacokinetics model, in situ single-pass intestinal perfusion model (SPIP), and MDCK II-MRP2 monolayer cell model to confirm the enhancement of QU or KA on IS absorption. Secondly, the effects of multidrug resistance-associated protein 2 (MRP2) inhibitors on the IS intestinal absorption were investigated to ascertain the mediation of MRP2 on IS absorption. Finally, the effects of QU or KA on MRP2 activity, protein expression, and mRNA level were performed by SPIP, everted-gut sacs, western blotting, and real-time polymerase chain reaction experiments to elucidate the related mechanisms. RESULTS: QU or KA increased IS intestinal absorption according to the increased AUC0-96h, Cmax, and Peff of IS after co-administrated with QU or KA to rats; the oral absorption of IS was mediated by MRP2 based on the facts that the average plasma concentration, AUC0-96h, and Peff of IS were increased when co-administrated with PR or MK571 (MRP2 inhibitors) as well as the Pratio(BL/AP) of IS was decreased by MK571 in MDCK II-MRP2 cell monolayer; the activity, protein expression, and mRNA level of MRP2 were inhibited or down-regulated by QU or KA because of the increased Peff of MRP2 substrate calcein (CA) and the down-regulated relative protein and mRNA intensity after co-treated with QU or KA. CONCLUSION: QU and KA increased the intestinal absorption of IS in TFH by regulating the activity and expression of MRP2, which provides useful information for the investigation of the transporter-mediated interaction of flavonoid components in herbal extracts.

Enhanced bioactivity and efficient delivery of quercetin through nanoliposomal encapsulation using rice bran phospholipids.

BACKGROUND: Quercetin is a phenolic compound occurring in many food plants and agricultural crops. It is reported to possess various health-promoting properties. However, the poor bioavailability of quercetin, due to its low aqueous solubility and its degradation during digestion, limits its nutraceutical applications. This study aimed to encapsulate quercetin in nanoliposomes using rice-bran phospholipids for its efficient delivery and controlled release, the protection of its structural stability, and enhancement of its bioactivity. RESULTS: Nanoliposomal encapsulation of quercetin by thin film-sonication method yielded spherical nanoparticles (157.33 ± 23.78 nm) with high encapsulation efficiency (84.92 ± 0.78%). Storage stability studies showed that nanoliposomal quercetin was stable at 4 °C and 27 °C for 6 and 5 months, respectively, as indicated by unchanged antioxidant activity and quercetin retention. Nanoliposomal quercetin showed a slow, limited release pattern in simulated gastric fluid (SGF), and an initial burst release followed by a slow constant releasing pattern in simulated intestinal fluid (SIF). A 1004-fold increase in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity was observed in quercetin nanoliposomes (SC50 = 4.04 ± 0.01 ppm) compared to non-encapsulated quercetin (SC50 = 4053.03 ± 5.61 ppm). Similarly, the anti-angiogenic activity of quercetin, as evaluated by duck embryo chorioallantoic membrane (CAM) assay, was enhanced twofold to fivefold by nanoliposomal encapsulation. CONCLUSION: This study showed that nanoliposomal encapsulation in rice-bran phospholipids enhanced the radical-scavenging and anti-angiogenic activities of quercetin. Furthermore, this study demonstrated that nanoliposomes can serve as efficient oral delivery system for quercetin. © 2018 Society of Chemical Industry.

Lecithin-Stabilized Polymeric Micelles (LsbPMs) for Delivering Quercetin: Pharmacokinetic Studies and Therapeutic Effects of Quercetin Alone and in Combination with Doxorubicin.

In this study, lecithin-stabilized polymeric micelles (LsbPMs) were prepared to load quercetin (QUE) in order to improve its bioavailability and increase its antitumor activity. Its combination with doxorubicin (DOX) to minimize DOX-mediated cardiac toxicity and increase the antitumor activity of QUE-loaded LsbPMs was also examined. LsbPMs were prepared following a previously reported procedure. Results demonstrated that optimal QUE-loaded LsbPMs contained quercetin, D-α-tocopheryl polyethylene glycol succinate, and lecithin at a weight ratio of 6:40:80. Drug-release studies showed that QUE released from LsbPMs followed a controlled release pattern. A cytotoxicity assay revealed that QUE-loaded LsbPMs had significant anticancer activities against MCF-7, SKBR-3, and MDA-MB-231 human breast cancer cells and CT26 mouse colon cancer cells. In animal studies, intravenous administration of QUE-loaded LsbPMs resulted in efficient growth inhibition of CT26 colon cancer cells in a Balb/c mice model. In a pharmacokinetics study compared to free QUE, intravenous and oral administration of QUE-loaded LsbPMs was found to have significantly increased the relative bioavailability to 158% and 360%, respectively, and the absolute bioavailability to 5.13%. The effect of QUE-loaded LsbPMs in combination with DOX resulted in efficient growth inhibition of CT26 colon cancer cells and reduced cardiac toxicity in the Balb/c mice model.

Enhancement of the solubility, stability and bioaccessibility of quercetin using protein-based excipient emulsions.

Emulsion-based excipient foods were developed to improve the bioaccessibility of an important hydrophobic nutraceutical: quercetin. Protein-stabilized oil-in-water excipient emulsions were prepared using sodium caseinate, whey protein isolate, or soy protein isolate as an emulsifier. These emulsions were then mixed with powdered quercetin and heated to simulate a cooking process. The excipient emulsions had relatively small droplet sizes (d < 270 nm) and remained stable against coalescence after exposure to boiling (100 °C for 60 min). In particular, casein was shown to be better at adsorbing to oil-water interface and contributed to a more stable interfacial layer than the other two proteins. Quercetin was solubilized in the emulsions during heating, which may be attributed to dissolution in the oil phase and complexation with proteins. There were appreciable differences in quercetin bioaccessibility in excipient emulsions stabilized by different emulsifiers (≈74% for casein, 54% for whey protein, 22% for soy protein, and 58% for Tween). This study suggests that milk proteins may be natural alternatives to synthetic surfactants for forming stable excipient emulsions capable of enhancing nutraceutical bioaccessibility.

CuS@MOF-Based Well-Designed Quercetin Delivery System for Chemo-Photothermal Therapy.

Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability, low water solubility, and chemical instability in the neutral and alkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the codelivery of quercetin as an anticancer agent and CuS nanoparticles as a photothermal therapy (PTT) agent for synergistic combination of chemotherapy and PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin and realize active-targeting drug delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from efficient internalization via FA-receptors-mediated endocytosis. The results of in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT agent can work together efficiently under NIR irradiation, thus remarkably improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8-QT multifunctional drug delivery system might be a promising nanoplatform for cancer treatment.

pH-sensitive and biocompatible quercetin-loaded GO-PEA-HA carrier improved antitumour efficiency and specificity.

A novel drug carrier was designed based on a new biomaterial, that is, graphene oxide (GO), to improve the efficiency and specificity of anticancer drug. In this study, GO was successively modified with polyetheramine (PEA) and hyaluronic acid (HA). The carrier was utilized to load an antitumor component, that is, quercetin (Que), which was derived from traditional Chinese medicine, namely the pagoda tree flower bud. This drug delivery system (DDS) exhibited pH sensibility under subacid condition and good biocompatibility even when GO concentration reached 350 µg/mL. Moreover, the antitumor efficacy was doubly improved and more long-acting compared with Que alone. Results show that the GO-based material has potential clinical applications for antitumor drug delivery.

Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations.

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing cinnamon oil as the oil phase, tween 80 and Carbitol® as the surfactant-cosurfactant mixture (Smix) and water as the aqueous phase containing 125 µg/200 µL of Quercetin was prepared by using spontaneous emulsification method. Nanoemulgel was prepared using 23% w/v poloxamer 407 as gel base. Comprehensive evaluation of the formulated nanoemulgel was carried out, and the optimized formulation was studied for drug release using Franz vertical diffusion cells. The formulated nanoemulgelexhibited a remarkable release of 92.4% of Quercetin at the end of 6 h, as compared to that of pure Quercetin-loaded gel (<3% release). The viscosity of the prepared nanoemulgel was found to be 30,647 ± 0.32 cPs at 37 °C. Also, molecular dynamics (MD) simulation was utilized to understand the gelation process and role of each component in the formulation. The present study revealed that the developed nanoemulgel of Quercetin could be a potential delivery system for clinical testing in periodontitis.

Nanostructured lipid carrier-based pH and temperature dual-responsive hydrogel composed of carboxymethyl chitosan and poloxamer for drug delivery.

The aim of this study was to develop a novel nanostructured lipid carrier (NLC) based dual-responsive hydrogel for ocular drug delivery of quercetin (QN). NLC loaded with quercetin (QN-NLC) was prepared using melt-emulsification combined with ultra-sonication technique. A three-factor five-level central composite design (CCD) was employed to optimize the formulation of QN-NLC. The optimized QN-NLC presented a particle size of 75.54nm with narrow size distribution and high encapsulation efficiency (97.14%).QN-NLC was characterized by TEM and DSC. In addition, a pH and temperature dual-responsive hydrogel composed of carboxymethyl chitosan (CMCS) and poloxamer 407(F127) was constructed by a cross-linking reaction with a naturally occurring nontoxic crosslinking agent genipin (GP). FT-IR was employed to demonstrate that F127/CMCS hydrogel was successfully synthesized. The results of SEM analysis and swelling experiments indicated that F127/CMCS hydrogel was both temperature-responsive and pH-responsive. From the results of In vitro release studies, dual temperature and pH responsiveness of the hydrogel was demonstrated, and 80.52% of total quercetin was released from the QN-NLC based hydrogel (QN-NLC-Gel) within 3days, revealing QN-NLC-Gel released drug sustainably. Taken together, the developed NLC-based hydrogel is a promising drug delivery system for the ophthalmic application.

Potential use of secondary products of the agri-food industry for topical formulations and comparative analysis of antioxidant activity of grape leaf polyphenols.

The aim of the present study was to develop a phytocosmetic using Vitis waste by-products, for use as a topical formulation for skin protection against ultraviolet radiation damage. The study also evaluates the free radical scavenger activity of the crude extracts of dried leaves of Vitis vinifera and Vitis labrusca, as well as the anthocyanins, flavonoid fraction and isolated compounds. Next, release and permeation studies of hydrogels were performed using Franz-type diffusion cells. Flavonoid acted more intensively in TRAP and conjugated dienes antioxidant assays, whereas anthocyanins had higher antioxidant activity in hydroxyl and nitric oxide assay. Only quercetin-3-O-glucuronide (5) was released from hydrogels, and the flavonoid retention in porcine ear skin after eight hours of permeation was below of limit of quantification for this compound. The polyphenols present in Vitis are capable of absorbing UV and visible light, justifying their potential as sunscreens for the development of a phytocosmetic.