Encapsulation Of Quercetin Research Articles

Effect of quercetin on lipid membrane rigidity: assessment by atomic force microscopy and molecular dynamics simulations

Quercetin (3,3ʹ,4ʹ,5,7-pentahydroxyl-flavone) is a natural flavonoid with many valuable biological effects, but its solubility in water is low, posing major limitations in applications. Quercetin encapsulation in liposomes increases its bioavailability; the drug effect on liposome elastic properties is required for formulation development. Here, we quantify the effect of quercetin molecules on the rigidity of lipoid E80 liposomes using atomic force microscopy (AFM) and molecular dynamics (MD) simulations. AFM images show no effect of quercetin molecules on liposomes morphology and structure. However, AFM force curves suggest that quercetin softens lipid membranes; the Young modulus measured for liposomes encapsulating quercetin is smaller than that determined for blank liposomes. We then used MD simulations to interpret the effect of quercetin on membrane rigidity in terms of molecular interactions. The decrease in membrane rigidity was confirmed by the simulations, which also revealed that quercetin affects structural and dynamic properties: membrane thickness is decreased, acyl chains disorder is increased, and diffusion coefficients of lipid molecules are also increased. Such changes appear to be related to the preferential localization of quercetin within the membrane, near the interface between the hydrophobic core and polar head groups of the lipids.

Impact of Quercetin Encapsulation with Added Phytosterols on Bilayer Membrane and Photothermal-Alteration of Novel Mixed Soy Lecithin-Based Liposome.

This study used highly lipophilic agents with an aim to increase the oxidant inhibitory activity and enhance photothermal stability of a novel mixed soy lecithin (ML)-based liposome by changing the composition of formulation within the membrane. Specifically, the development and optimization of the liposome intended for improving Trolox equivalent antioxidant capacity (TEAC) value and %TEAC loss was carried out by incorporating a natural antioxidant, quercetin (QU). In this context, a focus was set on QU encapsulation in ML-based liposomes and the concentration-dependent solubility of QU was investigated and calculated as encapsulation efficiency (EE). To explore the combined effects of the incorporation of plant sterols on the integrity and entrapment capacity of mixed phospholipid vesicles, conjugation of two types of phytosterols (PSs), namely β-sitosterol (βS) and stigmasterol (ST), to mixed membranes at different ratios was also performed. The EE measurement revealed that QU could be efficiently encapsulated in the stable ML-based liposome using 0.15 and 0.1 g/100 mL of βS and ST, respectively. The aforementioned liposome complex exhibited a considerable TEAC (197.23%) and enhanced TEAC loss (30.81%) when exposed to ultraviolet (UV) light (280–320 nm) over a 6 h duration. It appeared that the presence and type of PSs affect the membrane-integration characteristics as well as photodamage transformation of the ML-based liposome. The association of QU with either βS or ST in the formulation was justified by their synergistic effects on the enhancement of the EE of liposomes. Parallel to this, it was demonstrated that synergistic PS effects could be in effect in the maintenance of membrane order of the ML-based liposome. The findings presented in this study provided useful information for the development and production of stable QU-loaded ML-based liposomes for food and nutraceutical applications and could serve as a potential mixed lipids-based delivery system in the disease management using antioxidant therapy.

Development of Antioxidant-Loaded Nanoliposomes Employing Lecithins with Different Purity Grades.

This work focused on comparing the ability of lecithins with two purity grades regarding their performance in the development of nanoliposomes, as well as their ability to contain and release polar (trans-aconitic acid) and non-polar (quercetin) antioxidant compounds. First, the chemical characterization of both lecithins was carried out through infrared spectroscopy (FTIR), electrospray ionization mass spectrometry (ESI/MS), and modulated differential scanning calorimetry (mDSC). Second, nanoliposomes were prepared by the ethanol injection method and characterized by means of particle size, polydispersity, and zeta potential measurements. Third, the encapsulation efficiency and in vitro release profiles of antioxidants were evaluated. Finally, the antioxidant effect of quercetin and trans aconitic acid in the presence and absence of nanoliposomes was assessed through the oxygen radical absorbance capacity (ORAC) assay. The results showed that, although there are differences in the chemical composition between the two lecithins, these allow the development of nanoliposomes with very similar physicochemical features. Likewise, nanoliposomes elaborated with low purity grade lecithins favored the encapsulation and release of trans-aconitic acid (TAA), while the nanoliposomes made with high purity lecithins favored the encapsulation of quercetin (QCT) and modified its release. Regarding the antioxidant effect, the vehiculization of TAA and QCT in nanoliposomes led to an increase in the antioxidant capability, where QCT showed a sustained effect over time and TAA exhibited a rapidly decaying effect. Likewise, liposomal systems were also found to have a slight antioxidant effect.

Synthesis of quercetin-encapsulated alginate beads with their antioxidant and release kinetic studies

In this present study, different forms of quercetin encapsulated beads were synthesized, namely ionic cross-linked gel beads and cryogel beads. Fourier Transform Infrared (FT-IR) spectra of the beads were used to characterize and prove quercetin encapsulation in alginate beads. Swelling and drying profiles were studied. Besides, release kinetics of quercetin molecules from gel beads and cryogels were carefully investigated in two different solvent/media; dimethyl sulfoxide (DMSO) and Roswell Park Memorial Institute Medium (RPMI-1640). Based upon the release kinetic studies, it is found that quercetin release from alginate cryogel beads fits the first-order release model in DMSO and it depends on the concentration of quercetin in the beads. The release of quercetin from alginate gel beads was described by the Higuchi release model, which highlights the release of quercetin molecules through the pores of the matrix. In RPMI-1640, the release of quercetin from both forms of alginate beads fits zero-order release model and it indicates a constant release of quercetin per unit time. Finally, the radical scavenging activity of the quercetin quantities was tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, and successful results were obtained compared to reference material.

Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms.

Drugs have to overcome numerous barriers to reach their desired therapeutic targets. In several cases, drugs, especially the highly lipophilic molecules, suffer from low solubility and bioavailability and therefore their desired targeting is hampered. In addition, undesired metabolic products might be produced or off-targets could be recognized. Along these lines, nanopharmacology has provided new technological platforms, to overcome these boundaries. Specifically, numerous vehicle platforms such as cyclodextrins and calixarenes have been widely utilized to host lipophilic drugs such as antagonists of the angiotensin II AT1 receptor (AT1R), as well as quercetin and silibinin. The encapsulation of these drugs in supramolecules or other systems refines their solubility and metabolic stability, increases their selectivity and therefore decreases their effective dose and improves their therapeutic index. In this mini review we report on the formulations of silibinin and AT1R antagonist candesartan in a 2-HP-β-cyclodextrin host molecule, which displayed enhanced cytotoxicity and increased silibinin's and candesartan's stability, respectively. Moreover, we describe the encapsulation of quercetin in gold nanoparticles bearing a calixarene supramolecular host. Also, the encapsulation of temozolomide in a calixarene nanocapsule has been described. Finally, we report on the activity enhancement that has been achieved upon using these formulations as well as the analytical and computational methods we used to characterize these formulations and explore the molecular interactions between the host and quest molecules.

Layer-by-Layer Deposition of Hyaluronan and Quercetin-Loaded Chitosan Nanoparticles onto Titanium for Improving Blood Compatibility

Surface modification is an effective way to improve the hemocompatibility of biomaterials. Quercetin has significant anticoagulation and antithrombotic effects, and thus it is a promising candidate agent for the surface modification of blood-contacting materials. In this study, quercetin was successfully encapsulated in tripolyphosphate–chitosan nanoparticles (TCs) based on the ionic gelation of chitosan with tripolyphosphate (TPP) anions. Then, hyaluronan acid (HA)/quercetin-loaded TPP–chitosan nanoparticle (QTCs) films, in addition to HA/TCs films, were prepared separately using an electrostatic layer-by-layer self-assembly technique. The encapsulation of quercetin in the chitosan nanoparticles was confirmed by UV spectra. The quercetin-loaded multilayer coatings were also successfully self-assembled, as confirmed by the UV spectra and contact angle measurements. Platelet adhesion experiments were carried out with platelet-enriched plasma so as to evaluate the blood compatibility of the different samples. There were many platelets on the surfaces of the glass and HA/TC-coated titanium, which were partially activated but not aggregated. Meanwhile, many more platelets were observed on the uncoated titanium surfaces, most of which developed pseudopodia. By contrast, the platelet adhesion and activation were reduced remarkably on the surface of the HA/QTC-coated titanium. These results showed that the multilayer coatings containing quercetin could act as potential biomaterials to improve the anticoagulation performance of blood-contacting materials.

Development and optimization of stealth liposomal system for enhanced in vitro cytotoxic effect of quercetin

The present study was designed to develop a stealth liposomal drug delivery system for a naturally occurring flavonoid, quercetin. Quercetin is a unique polyphenol with multifarious curative applications, anticancer activity being one of them. However, the poor aqueous solubility of this hydrophobic compound hinders its therapeutic effects. For this purpose, our study aimed to enhance the aqueous solubility and in vitro cytotoxic efficacy of quercetin by its incorporation in stealth liposomal formulation. Quercetin-loaded stealth liposomes were prepared with different molar ratios of egg-PC, cholesterol and DSPE-PEG2000 lipids by the traditional thin film hydration method followed by their physicochemical characterization to determine average particle size, polydispersity index (PDI) and zeta potential. The encapsulation efficiency (EE%), saturation solubility of quercetin and apparent solubility of quercetin-loaded stealth liposomes were determined using HPLC. The stealth liposomes were investigated for their stability and an optimized and stable liposomal formulation containing 5% DSPE-PEG2000 lipid was then further evaluated for its in vitro cytotoxicity in HeLa cells and compared to that of free quercetin. The average particle size, PDI, zeta potential and EE% of the optimized liposomes were found to be 110 nm, 0.169, −3.69 mV and 89%, respectively. Encapsulation of quercetin in the stealth liposomal system significantly increased its solubility by approximately 44-fold. This liposomal formulation was stable up to 21 days in terms of its physicochemical characteristics and EE%. Liposomal encapsulation of quercetin was significantly more capable of reducing cell viability of HeLa cells when compared to free quercetin. Our study suggests that this appropriately designed stealth liposomal system could be a promising carrier for encapsulation of the hydrophobic bioactive, quercetin, and significantly enhanced the aqueous solubility and escalated the cytotoxic efficacy of quercetin in cervical cancer cells.

Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma

The present study aims to formulate quercetin loaded liquid crystalline nanoparticles (LCN) and surface modified liquid crystalline nanoparticles (sm-LCN) as well as investigate their anti-inflammatory activity in human primary bronchial epithelial cell line (BCi-NS1.1) induced with lipopolysaccharide (LPS). Quercetin LCN were prepared using ultrasonication method. The formulated LCNs and sm-LCNs were characterised in terms of particle size, zeta potential as well as the drug encapsulation efficiency. Furthermore, their morphology and in vitro release profile were also studied. In addition, the anti-inflammatory activity of quercetin LCN and sm-LCNs were evaluated by measuring the concentration of pro-inflammatory markers namely interleukin (IL)-1β, IL-6 and IL-8 in BCI-NS1.1 cell lines via cytometric bead array. The molecular mechanism inherent to the inclusion of quercetin into monoolein nanosystem and surface modification of the nanosystem with chitosan was elucidated via molecular mechanics simulations. Quercetin LCN and sm-LCN significantly (p < 0.05) decreased the production of IL-1β, IL-6 and IL-8 compared to LPS only group. Encapsulation of quercetin into LCN and sm-LCN further enhanced its anti-inflammatory activity compared to quercetin in dimethyl sulfoxide (DMSO). In addition to that, quercetin LCN and sm-LCN also exhibited comparable activity to fluticasone in terms of significantly (p < 0.05) reducing the production of IL-1β and IL-6. Quercetin loaded LCN and sm-LCN could be a potential therapeutic intervention for asthma as they are efficacious in suppressing the production of key pro-inflammatory cytokines associated with the development of asthma.

Encapsulation of quercetin-loaded β-lactoglobulin for drug delivery using modified anti-solvent method

Many scientists use proteins as attractive bio-availability enhancers for natural compounds and pharmaceuticals which have poor water solubility, due to their natural abundance, amphiphilic nature, and desirable biocompatibility. Here, we investigate the preparation, characterization, and application of β-Lactoglobulin (BLG) based nanoparticles for encapsulation of quercetin, systematically. We used anti-solvent method that is common for nano particle preparation of water-soluble proteins. The procedure involves partial unfolding of protein molecules, limited aggregation in the presence of anti-solvent, crosslinking via chemical linker, and refolding of the constituent monomers. The results showed that acetone anti-solvent has significant effect on accumulation of BLG-quercetin nanoparticles. Adjustment of acetone content to the value of 10% v/v (acetone/water) followed by mild evaporation led to a notable improvement in Encapsulation Efficiency (EE%) and Loading Efficiency (LE%), which raised LE to 13.9%. In addition, reducing glutaraldehyde amount to 50% of equivalent, led to toxicity reduction of the drug carrier system. The nanoparticles with a mean particle size of about 180–300 nm and semispherical appearance were approved using Atomic Force Microscopic (AFM) and Field Emission Scanning Electron Microscopy (FESEM) methods. Protein nanoparticles may be digested at different stages of the gastrointestinal tract, depending on acidity, ionic strength, or specificity of proteases (pepsin and trypsin). This study suggested that BLG as a resistant protein to peptic digestion forms nanoparticles that are digestible (compared to untreated BLG) by pepsin. As a result, satisfactory controlled release was achieved under simulated fast condition, i.e., digestion in simulated gastric fluid (SGF) at pH = 2 and then in simulated intestinal fluid (SIF). Finally, the mechanism of drug release into the buffer environment was well-fitted by the Korsmeyear-Peppas kinetic model. The conclusions of this study may apply not only to quercetin-BLG system, but also to a wide variety of encapsulation systems involving water-soluble protein and hydrophobic target compound, with adequate LE and reduced toxicity.

Development and characterization of alginate / chitosan nanoparticulate system for hydrophobic drug encapsulation

The present study was emphasized to develop Alginate/Chitosan nanoparticles capable of working as carriers of the hydrophobic drug quercetin, a polyphenolic nutraceutical belonging to flavonoid category of natural compounds, with multifaceted therapeutic applications. Accordingly, quercetin loaded nanoparticles was prepared by an ionotropic gelation of chitosan with sodium tripolyphosphate, followed by alginate polyelectrolyte complexation. Synthesised unloaded and quercetin loaded Alginate/Chitosan nanoparticles were extensively characterised for their intermolecular interaction, morphology, percentage of encapsulation and loading capacity of the drug by various physiochemical characterization techniques such as ATR-FTIR, SEM, TEM, and XRD. The nanoparticles showed excellent architecture with an average particle size of 118–255 nm, showing 82.4% of quercetin encapsulation and 46.5% of quercetin loading capacity. Our results imply that the formulated Alginate/Chitosan nanoparticles could be a promising carrier for the encapsulation of the hydrophobic bioactive compound combining safety profile with no acute systemic toxicity in animal models and enhanced protective activity of quercetin.

Fabrication of stable zein nanoparticles coated with soluble soybean polysaccharide for encapsulation of quercetin

The present work aims to prepare and stabilize zein colloidal nanoparticles using soluble soybean polysaccharide (SSPS) as a stabilizer. A simple antisolvent precipitation method was used to fabricate the zein/SSPS composite nanoparticles at pH 4.0. The results showed that the SSPS-stabilized zein nanoparticles (size around 200 nm, PDI below 0.2) did not aggregate or precipitate at pH 2.0–8.0. And they were also relatively stable for elevated ionic strength and high temperature. Affected by the SSPS coating, the surface hydrophobicity of the zein nanoparticles decreased over a wide pH range. Conditions of forming zein/SSPS nanoparticles were successfully used to encapsulate hydrophobic quercetin (Q). The encapsulation efficiency was greatly improved to 82.5% after SSPS coating, compared to 59.2% for the zein without coating. Besides, the photochemical stability and ABTS+ scavenging ability of Q in zein/SSPS composite nanoparticles were significantly enhanced. This study demonstrates that these composite nanoparticles can be used as all-natural delivery systems for bioactive molecules in food and pharmaceutical formulations.

Novel findings for quercetin encapsulation and preservation with cyclodextrins, liposomes, and drug-in-cyclodextrin-in-liposomes

The low solubility, poor bioavailability, and low chemical stability of quercetin (Quer) are the main drawbacks that limit its use as a food nutraceutical. In this study, the encapsulation in cyclodextrins (CDs), conventional liposomes (CLs), and drug-in-cyclodextrin-in-liposomes (DCLs) was conducted in order to improve the physicochemical properties of Quer. Phase solubility studies revealed an enhancement of Quer solubility upon complexation with various CDs. CLs composed of three different types of phospholipids (unsaturated egg Lipoid E80, unsaturated soybean Lipoid S100, and saturated soybean Phospholipon 90H) as well as DCLs were prepared by ethanol injection method and characterized. Liposomes constituted of Lipoid E80 showed small diameter, narrow size distribution, and higher encapsulation efficiency of Quer compared to the two other CLs. The photostability of Quer-loaded liposomes was also evaluated. Results show that Lipoid E80-liposomes allow a better protection of Quer against UV irradiation than those prepared using other lipids. This effect could be explained by their different membrane rigidity as determined by Atomic Force Microscopy (AFM). Moreover, the photostability of Quer was additionally improved when encapsulated in DCLs (SBE-β-CD/Quer inclusion complex in Lipoid E80 liposomes), in comparison to CLs. The same trend was obtained regarding the Quer stability in simulated gastrointestinal fluids. Finally, all liposome formulations were physically stable after 1 year of storage at 4 °C.

Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment

The study aims for development of an efficient polymeric carrier for evaluating pharmaceutical potentialities in modulating the drug profile of quercetin (QUE) in anti-diabetic research. Alginate and succinyl chitosan are focused in this investigation for encapsulating quercetin into core-shell nanoparticles through ionic cross linking. The FT-IR, XRD, NMR, SEM, TEM, drug entrapment and loading efficiency are commenced to examine the efficacy of the prepared nanoparticles in successful quercetin delivery. Obtained results showed the minimum particle size of ∼91.58nm and ∼95% quercetin encapsulation efficiently of the particles with significant pH sensitivity. Kinetics of drug release suggested self-sustained QUE release following the non-fickian trend. A pronounced hypoglycaemic effect and efficient maintenance of glucose homeostasis was evident in diabetic rat after peroral delivery of these quercetin nanoparticles in comparison to free oral quercetin. This suggests the fabrication of an efficient carrier of oral quercetin for diabetes treatment.

In vitro protective effects of encapsulated quercetin in neuronal models of oxidative stress injury

ABSTRACTThe aim of the present study was to evaluate the protective effects of free and encapsulated quercetin against oxidative stress injury in neuronal SH-SY5Y cells and isolated rat brain synaptosomes. Quercetin (QR) was encapsulated in nanoparticles consisting of sodium alginate and chitosan and the ratio between both biopolymers was 10:1 or 1:10, respectively. The nanoparticles formulated with higher amount of sodium alginate were negatively charged, whereas those with higher chitosan amount were positively charged. The protective effects of free and encapsulated quercetin were studied in two in vitro models: H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells and 6-hydroxydopamine (6-OHDA) induced neurotoxicity in isolated rat brain synaptosomes. Comparing to free quercetin, quercetin encapsulated in the nanoparticles formulated with higher chitosan concentration exerted more pronounced neuroprotective activity in a model of H2O2-induced (1 mmol/L H2O2, 15 min) oxidative stress in neuroblastoma SH-SY5Y cells. A similar trend was observed in a model of 6-OHDA induced neurotoxicity in rat brain synaptosomes. In conclusion, encapsulation of quercetin in nanoparticles based predominantly on chitosan improved its neuroprotective activity in vitro.

Nanostructured lipid carrier (NLC) as a strategy for encapsulation of quercetin and linseed oil: Preparation and in vitro characterization studies

Due to their poor solubility in hydrophilic matrices and chemical instability, the applications of quercetin and linseed oil in functional foods are limited. In this work we have encapsulated quercetin and linseed oil into NLC by high pressure homogenization technique. Quercetin and linseed oil co-loaded nanoparticles were less than 100 nm in diameter and spherical in shape. Nano-encapsulated quercetin was found to be presented in NLC with less ordered lipid cores as an encapsulated amorphous form. And the solubility of quercetin in hydrophilic matrices consisted of linseed oil and surfactants was improved by at least 1300 folds. The addition of linseed oil improved the in vitro antioxidant activities of quercetin loaded NLCs. Besides, the in vitro release of quercetin from NLC exhibited a sustained pattern. Lower lipid oxidation was found in quercetin and linseed oil co-loaded NLC compared with conventional linseed oil emulsion. Finally, storage study indicated that the fabricated NLCs were stable for more than 3 months at 25 °C. In conclusion, NLC could be a promising vehicle for delivery of hydrophobic bioactive compounds and ω-3 unsaturated fatty acids in food industry.

Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10μg/ml) significantly attenuated the decrease in cell viability in H2О2-induced oxidative stress (0.1mM H2О2), thus showing an effective in vitro protection.In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol − induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18mg/kg b.w., 7days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury.

Encapsulation of quercetin in liposomes by ethanol injection and physicochemical characterization of dispersions and lyophilized vesicles

Abstract Quercetin is a flavonoid with high antioxidant capacity that provides beneficial biological effects. However, the absorption rate of quercetin in the gastrointestinal tract is low but encapsulated lipid matrices, such as liposomes, can be useful to enhance its bioavailability. In this study, quercetin-loaded liposome dispersions were produced by ethanol injection and 12 mM of phospholipid encapsulating 0.3% molar quercetin was suitable to evaluate physicochemical stability. The Langmuir monolayer technique indicated that it was possible to encapsulate a maximum of 0.3% molar quercetin in liposomes. Quercetin-loaded liposome dispersions presented a mean hydrodynamic diameter of 264 nm and a zeta potential of −17 mV, which is typical for small unilamellar vesicles produced by ethanol injection. Sucrose was used as the lyoprotectant (mass sucrose: phospholipid ratio, 4:1), and the encapsulated quercetin had not degraded after 100 days of storage. In addition, the lyophilized liposomes presented a low propensity for water adsorption and low hygroscopicity. Such behavior is considered highly suitable for stability in dried foods.

Quercetin loaded particles production by means of supercritical fluid extraction of emulsions: Process scale-upstudy and thermo-economic evaluation

Quercetin is an antioxidant compound with promising activity against a wide variety of diseases. However, a major limitation for the clinical application of quercetin is its low bioavailability, due to its low solubility in water. One way to increase the bioavailability of quercetin is to precipitate it in sub-micrometricscale, encapsulated by a surfactant material, using the Supercritical Fluid Extraction of Emulsions (SFEE) method. The objective of this work is to study the scale-up of a semi-continuous SFEE process for the production of microencapsulated quercetin. An experimental study of the encapsulation of quercetin in soy-bean lecithin–Pluronic L64®surfactants was performed in order to evaluate the variation of product characteristics with significant parameters, such as duration of SFEE, density of CO2 medium, used CO2/L of emulsion (kg/L), and thus determine the suitable conditions for scale-up. In addition, a themo-economic evaluation was done in order to identify bottlenecks during scale-up and promote solutions. According to the thermo-economic evaluation, the decrease of CO2 flow demonstrated to be the main parameter to decrease the energy demand and cost of manufacturing of the SFEE process. Thus further experimental studies should be done towards optimization of this parameter.

Dermal quercetin lipid nanocapsules: Influence of the formulation on antioxidant activity and cellular protection against hydrogen peroxide

Quercetin is a plant flavonoid with strong antioxidant and antiinflammatory properties interesting for skin protection. However, its poor water solubility limits its penetration and so its efficiency on skin. For this purpose, quercetin lipid nanocapsules were formulated implementing phase inversion technique wherein several modifications were introduced to enhance quercetin loading. Quercetin lipid nanocapsules were formulated with two particle size range, (50nm and 20nm) allowing a drug loading of 18.6 and 32mM respectively. The successful encapsulation of quercetin within lipid nanocapsules increased its apparent water solubility by more than 5000 fold (from 0.5μg/ml to about 5mg/ml). The physicochemical properties of these formulations such as surface charge, stability and morphology were characterized. Lipid nanocapsules had spherical shape and were stable for 28days at 25°C. Quercetin release from lipid nanocapsules was studied and revealed a prolonged release kinetics during 24h. Using DPPH assay, we demonstrated that the formulation process of lipid nanocapsules did not modify the antioxidant activity of quercetin in vitro (92.3%). With the goal of a future dermal application, quercetin lipid nanocapsules were applied to THP-1 monocytes and proved the cellular safety of the formulation up to 2μg/ml of quercetin. Finally, formulated quercetin was as efficient as the crude form in the protection of THP-1 cells from oxidative stress by exogenous hydrogen peroxide. With its lipophilic nature and occlusive effect on skin, lipid nanocapsules present a promising strategy to deliver quercetin to skin tissue and can be of value for other poorly water soluble drug candidates.

Synthesis and characterization of polyhydroxybutyrate-co-hydroxyvalerate nanoparticles for encapsulation of quercetin

Polyhydroxybutyrate- co-hydroxyvalerate has been identified as a useful polymer for biomedical application due to its biocompatibility and processability. Polyhydroxybutyrate- co-hydroxyvalerate nanoparticles loaded with quercetin, an antimicrobial, anti-inflammatory, and antiviral polyphenol with limited solubility, were obtained using a high-speed double-emulsion technique. The nanoparticle size and the dissolution of quercetin were controlled simultaneously through high-speed stirring (15,000 r/min) in the emulsification process. The size range of quercetin-loaded polyhydroxybutyrate- co-hydroxyvalerate nanoparticles was between 250 and 650 nm. Spherical shape with no aggregation of nanoparticles was confirmed by electron microscopy. Loaded nanoparticles showed less thermal degradation than unloaded nanoparticles. An encapsulation efficiency of 51% was found. Most of the quercetin was released from the nanoparticles within the first 5 h of water immersion. A biocompatibility analysis of the nanoparticles showed no cytotoxicity and no significant difference between loaded and unloaded nanoparticles.