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The mass transport effect of aqueous micelles on antioxidants and oxidation products in emulsions may alter the rate, degree, and pathway of lipid oxidation. In this study, the dynamic mass transport of oxidation products and endogenous tocopherol during storage at different micelle concentrations was monitored by UV-vis spectrophotometry and high-performance liquid chromatography. Furthermore, the microlocalization of tocopherol in micelles was investigated using 1 H nuclear magnetic resonance and nuclear Overhauser effect spectroscopy, fluorescence measurements, and molecular dynamics simulation. It was demonstrated that high-concentration micelles enhanced the emulsion stability by promoting the mass transport of hydroperoxides and endogenous antioxidants. The enhancement of micelles was a superposition effect of concentration, interaction sites, and binding force between tocopherols and Tween 20 molecules. Tween 20 concentration-induced favorable changes of microlocalization of tocopherol and dynamic mass transport demonstrated a new integrated perspective to control lipid oxidation.

In this study, the digestive properties of milk formulas (two concept milk formulas L1 and L2 with D 4,3 ∼5 μm and a control milk formula S1 with D 4,3 ∼0.5 μm) were evaluated using a dynamic digestion model simulating the infant gastrointestinal tract. The results showed that L1 and L2 had a lower lipolysis degree compared to S1 during gastric digestion and no significant difference at the end of the digestion process. Triacylglycerol lipolysis products were highly related to the lipid sources of milk formulas. At the end of digestion, glycerophospholipids in milk formulas were hydrolyzed to lysophospholipids (∼60-80%), while sphingomyelins were barely hydrolyzed. Concept milk formulas showed a complete spherical structure with a mean size of 3-5 μm during gastric digestion, while the control formula had large aggregates consisting of small lipid droplets. This study reveals that the structure of lipid droplets moderates the gastric digestion emulsion structure and further influences the digestive properties of milk formulas.

The aim of the presented study was to evaluate the release of the enzymatically initiated production of hexanal from double emulsion electrospun bio-active membranes at a temperature of fruit storage. Among different formulations of water-in-oil (W1/O) primary emulsions, the emulsion composed of 12% w/v Tween20 and 0.1 M NaCl in water (W1) and 6% of poly(glycerol) poly(ricinoleate) dissolved in sunflower oil (O) using W1/O ratio of 80/20 (w/w) (Tween20-NaCl/6% PGPR) was selected, for further incorporation of enzymes, based on the lowest average droplet size (391.0 ± 15.6 nm), low polydispersity index (0.255 ± 0.07), and good gravitational stability also after 14 days. Both enzymes, lipase and lipoxygenase are needed to produce hexanal (up to 58 mg/L). Additionally, double emulsions were prepared with sufficient conductivity and viscosity using different W1/O to W2 ratios for electrospinning. From the selected electrospun membrane, up to 4.5 mg/L of hexanal was released even after 92 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rutin is a polyphenol with beneficial pharmacological properties. However, its bioavailability is often compromised due to low solubility and poor stability. Encapsulation technologies, such as emulsion systems, have been proven to be promising delivery vehicles for enhancing the bioavailability of bioactive compounds. Thus, this study was proposed and designed to investigate the colonic targeting and colonic fermentation characteristics of rutin-loaded ovalbumin-ferulic acid-polysaccharide (OVA-FA-PS) complex emulsions. The results indicate that OVA-FA-PS emulsion effectively inhibits the degradation of rutin active substances and facilitates its transport of rutin to the colon. The analysis revealed that the OVA-FA-κ-carrageenan emulsion loaded with rutin exhibited superior elasticity and colon targeting properties compared to the OVA-FA-hyaluronic acid or OVA-FA-sodium alginate emulsions loaded with rutin in the composite emulsion. Additionally, it was observed that the rutin loaded within the OVA-FA-κ-carrageenan emulsion underwent degradation and was converted to 4-hydroxybenzoic acid during colonic fermentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

21-Hydroxy-20-methylpregn-4-en-3-one (4-HBC, bisnoralcohol) is a crucial intermediate for the synthesis of steroidal drugs. Significant challenges including by-products formation and poor substrate solubility were still confronted in its main synthetic route by microbial conversion from phytosterol. Construction of a direct bioconversion pathway to 4-HBC and an efficient substrate emulsion system is therefore urgently required. In this study, three novel isoenzymes of 3-ketosteroid-Δ 1 -dehydrogenase (KstD) and 3-ketosteroid 9α-hydroxylase (KsH) in Mycobacterium neoaurum were excavated and identified as KstD4, KstD5, and KsHA3. A strain capable of fully directing the synthesis of 4-HBC was metabolically engineered via serial genetic deletion combined with enhanced expression of cholesterol oxidase (ChOx2) and enoyl-CoA hydratase (EchA19). Moreover, a micro-emulsion system combined with soybean oil and hydroxypropyl-β-cyclodextrin improved substrate solubility and bioavailability. In batch fermentation, molar yield of 96.7% with 39.5 g L -1 4-HBC was obtained from 50 g L -1 phytosterol. Our findings demonstrate the potential for industrial-scale biosynthesis of 4-HBC., (© 2024 Wiley‐VCH GmbH.)

This study investigates the potential of a quercetin-based emulsion system to moderate starch digestion and manage blood glucose levels, addressing the lack of in vivo research. By enhancing quercetin bioaccessibility and targeting release in the small intestine, the emulsion system demonstrates significant inhibition of starch digestion and glucose spikes through both in vitro and in vivo experiments. The system inhibits α-amylase and α-glucosidase via competitive and mixed inhibition mechanisms, primarily involving hydrogen bonds and van der Waals forces, leading to static fluorescence quenching. Additionally, this system downregulates the protein expression and gene transcription of SGLT1 and GLUT2. These findings offer a novel approach to sustaining glucose equilibrium, providing a valuable foundation for further application of quercetin emulsion in food science., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pickering emulsions stabilized by multicomponent particles have attracted increasing attention. Research on characterizing the digestion and health benefit effects of these emulsions in the human gastrointestinal tract are quite limited. This work aims to reveal the digestive characteristics of media-milled purple sweet potato particle-stabilized Pickering emulsions (PSPP-Es) during in vitro digestion and colonic fermentation., Results: The media-milling process improved the in vitro digestibility and fermentability of PSPP-Es by reaching afree fatty acids release rate of 43.11 ± 4.61% after gastrointestinal digestion and total phenolic content release of 101.00 ± 1.44 μg gallic acid equivalents/mL after fermentation. In addition, PSPP-Es exhibited good antioxidative activity (2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays), α-glucosidase inhibitory activity (half-maximal inhibitory concentration: 6.70%, v/v), and prebiotic effects, reaching a total short-chain fatty acids production of 9.90 ± 0.12 mol L -1 , boosting the growth of Akkermansia, Bifidobacterium, and Blautia and inhibiting the growth of Escherichia-Shigella., Conclusions: These findings indicate that the media-milling process enhances the potential health benefits of purple sweet potato particle-stabilized Pickering emulsions, which is beneficial for their application as a bioactive component delivery system in food and pharmaceutical products. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The present study focused on investigating the stability and in vitro simulation characteristics of oil-in-water (O/W) and oleogel-in-water (Og/W) emulsions. Compared with O/W emulsion, the Og/W emulsion exhibited superior stability, with a more evenly spread droplet distribution, and the Og/W emulsion containing 3 % hemp seed protein (HSP) showed better stability against environmental factors, including heat treatment, ionic strength, and changes in pH. Additionally, the stability of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabinol (CBN) and the in vitro digestion of hemp seed oil (HSO) were evaluated. The half-life of CBN in the Og/W emulsion was found to be 131.82 days, with a degradation rate of 0.00527. The in vitro simulation results indicated that the Og/W emulsion effectively delayed the intestinal digestion of HSO, and the bioaccessibility of Δ 9 -THC and CBN reached 56.0 % and 58.0 %, respectively. The study findings demonstrated that the Og/W emulsion constructed with oleogel and HSP, exhibited excellent stability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Biosurfactants are in demand by the global market as natural commodities suitable for incorporation into commercial products or utilization in environmental applications. Fungi are promising producers of these molecules and have garnered interest also for their metabolic capabilities in efficiently utilizing recalcitrant and complex substrates, like hydrocarbons, plastic, etc. Within this framework, biosurfactants produced by two Fusarium solani fungal strains, isolated from plastic waste-contaminated landfill soils, were analyzed. Mycelia of these fungi were grown in the presence of 5% olive oil to drive biosurfactant production. The characterization of the emulsifying and surfactant capacity of these extracts highlighted that two different components are involved. A protein was purified and identified as a CFEM (common in fungal extracellular membrane) containing domain, revealing a good propensity to stabilize emulsions only in its aggregate form. On the other hand, an unidentified cationic smaller molecule exhibits the ability to reduce surface tension. Based on the 3D structural model of the protein, a plausible mechanism for the formation of very stable aggregates, endowed with the emulsifying ability, is proposed. KEY POINTS: • Two Fusarium solani strains are analyzed for their surfactant production. • A cationic surfactant is produced, exhibiting the ability to remarkably reduce surface tension. • An identified protein reveals a good propensity to stabilize emulsions only in its aggregate form., (© 2024. The Author(s).)

Tyrosinase is capable of oxidizing tyrosine residues in proteins, leading to intermolecular protein cross-linking, which could modify the protein network of food and improve the texture of food. To obtain the recombinant tyrosinase with microbial cell factory instead of isolation tyrosinase from the mushroom Agaricus bisporus , a TYR expression cassette was constructed in this study. The expression cassette was electroporated into Trichoderma reesei Rut-C30 and integrated into its genome, resulting in a recombinant strain C30-TYR. After induction with microcrystalline cellulose for 7 days, recombinant tyrosinase could be successfully expressed and secreted by C30-TYR, corresponding to approximately 2.16 g/L tyrosinase in shake-flask cultures. The recombinant TYR was purified by ammonium sulfate precipitation and gel filtration, and the biological activity of purified TYR was 45.6 U/mL. The purified TYR could catalyze the cross-linking of glycinin, and the emulsion stability index of TYR-treated glycinin emulsion was increased by 30.6% compared with the untreated one. The cross-linking of soy glycinin by TYR resulted in altered properties of oil-in-water emulsions compared to emulsions stabilized by native glycinin. Therefore, cross-linking with this recombinant tyrosinase is a feasible approach to improve the properties of protein-stabilized emulsions and gels.

In this work, the effects of whey protein-carboxymethyl cellulose (WP-CMC) conjugates on the environmental stability, in vitro digestion stability, storage stability and bioaccessibility of high internal phase emulsions (HIPEs) were investigated. Compared to the HIPEs stabilized by the mixture of WP and CMC, the HIPEs stabilized by WP-CMC were less sensitive to environmental changes by particle size and zeta-potential, and showed better stability and bioavailability of pine nut oil as well as β-carotene during simulated gastrointestinal digestion. In addition, the inclusion function and pine nut oil oxidative stability of the HIPEs stabilized by WP-CMC were better during 16 days of storage than those of the pine nut oil and HIPEs stabilized by the mixture of WP and CMC, and also expressed higher storage stability of β-carotene. These results suggested that the conjugate-stabilized emulsions developed in this study have potential applications as protectors and carriers of liposoluble active ingredients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hypothesis: Oleosomes are natural oil droplets with a unique phospholipid/protein membrane, abundant in plant seeds, from which they can be extracted and used in emulsion-based materials, such as foods, cosmetics and pharmaceutics. The lubrication properties of such materials are essential, on one hand, due to the importance of the in-mouth creaminess for the consumed products or the importance of spreading the topical creams. Therefore, here, we will evaluate the lubrication properties of oleosomes, and how these properties are affected by the components at the oleosome membrane., Experiment: Oleosomes were extracted, and their oral lubricating properties were evaluated using tribology. To understand the influence of the oil droplet membrane composition, reconstituted oleosomes were also studied, with membranes that differed in protein/lecithin ratio. Additionally, whey protein- and lecithin-stabilised emulsions were used as reference samples. Confocal laser scattering microscopy was used to study the samples visually before and after tribological analysis., Findings: Oleosomes followed a ball-bearing mechanism, which was probably related to their high physical stability due to the presence of membrane proteins. When the membrane protein concentration at the surface was reduced, the droplet stability weakened, leading to plating-out lubrication. Following our results, we elucidated the oleosome lubrication mechanism and showed their possible control by changing the membrane composition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Increasing attentions are paid to high internal phase emulsions (HIPEs) due to their unique properties. In this study, pea protein-based fibrils were used as emulsifier to stabilize HIPEs. We demonstrated that the molecular assembly pathway and interfacial behavior of pea protein-based fibrils are affected by ionic strength. And the increased abundance of highly flexible worm-like nanofibrils facilitated their adsorption and packing on oil droplets, resulting in improved emulsion properties to stabilize the HIPEs with the internal phase volume fraction as high as 90%. Based on this, high loading content of carotenoids up to 0.05 wt% in the prepared HIPEs, protection of their stability against heating, UV and iron ions, and significantly increased bio-accessibilities of the carotenoids were realized. Animal studies using a mouse model of DSS-induced colitis revealed that carotenoid loaded HIPEs can alleviate the colon injury, by downregulating the expression of inflammatory cytokines, and promoting intestinal barrier function. This work will deepen the understanding of the formation of pea protein fibrils and provide a reference for the rational use of carotenoid loaded HIPEs in IBD management.

The objective of this study was to explore the benefits of transdermal drug delivery systems as an alternative option for patients who are unable to tolerate oral administration of drugs, such as ibuprofen (IB). To achieve this, nonionic surfactants and three cosolvents were employed to develop new microemulsions (MEs) that contained IB as nanocarriers. The aim was to enhance the solubility and bioavailability of the drug after transdermal administration. The MEs were characterised by droplet size, polydispersity index (PDI), and rheological properties. Furthermore, the flux of IB was evaluated by Franz diffusion cells using excised rat skin and in vivo bioavailability using rats. The results showed that the MEs had ideal viscosity and droplet size below 100 nm. Moreover, using the developed MEs, an improvement in the solubility (170 mg/mL) and flux through the rat skin (94.6 ± 8.0 µg/cm 2 .h) was achieved. In addition, IB demonstrated a maximum plasma level of 0.064 mg/mL after 8 h of transdermal administration in rats using the ME with an increase in the bioavailability of about 1.5 times in comparison to the commercial IB gel. In conclusion, the developed nonionic MEs containing IB can be ideal nanocarriers and promising formulations for the transdermal administration of IB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The thermal acidic-treatment-induced fibrillation of legume proteins isolated from cowpea and mung bean was demonstrated to be promoted by salt. Worm-like thin prefibrilar intermediates were formed in low salt concentrations (0-75 mM), which twisted to be the thick and mature amyloid-like fibrils with multistrands as the salt content was elevated (150-300 mM). Absorption of the fibrils fabricated in high salt concentrations to the oil/water interface constructed the protein layer with a significantly higher interfacial modulus compared with the one formed by the fibrils fabricated in low salt concentrations. Consequently, they showed the superiority in stabilizing high internal phase emulsions (HIPEs) with oil volume fraction ratios higher than 74%. HIPEs stabilized by the high salt-concentration-induced legume protein fibrils had stronger capabilities not only in encapsulating liposoluble carotenoids but also in protecting their stability against heating, ultraviolet, and iron ion stimulus, compared with the one stabilized by the low-salt-concentration-induced legume protein fibrils. Bioaccessibilities of the carotenoids in simulating gastrointestinal (GI) digestion were significantly improved after encapsulation by the HIPEs, which were interestingly increased with the elevation of salt concentrations utilized for preparing the legume protein fibrils. Furthermore, the carotenoids-loading-HIPEs were injectable and showed in vivo nutritional functions of mitigating colitis.

In the current study, the solubility and permeability of Osthole-loaded microemulsion were enhanced, which increased bioavailability. In addition, Carbomer 940 was added for prolonged drug delivery. The microemulsion was prepared after the screening of Kukui oil, Labrasol (surfactant), and transcutol-P (co-surfactant). Pseudoternary phase diagrams were employed to find the microemulsion region. Box Behnken Design (BBD) was employed for optimizing microemulsions. Variables were related and compared using mathematical equations and response surface plots (RSP). MEBG was then compared with control gel on the basis of stability studies, drug permeation, skin irritation studies, and anti-inflammatory studies. Microemulsion preparations depicted a pH of 5.27 - 5.80, a conductivity of 139 - 185 μS/cm, a poly-dispersity index of 0.116 - 0.388, a refractive index of 1.330 - 1.427, an average droplet size of 64 - 89 nm, homogeneity, spherical shape, viscosity 52 - 185 cP. Predicted values of Optimized microemulsions showed more reasonable agreement than experimental values. The microemulsion was stable and non-irritating on Rabbit skin. MEBG showed a significant difference from control gel for percent edema inhibition from the standard. The permeation enhancing capability of MEBG using a suitable viscosity fabricates it promising carrier for transdermal delivery of Osthole.

Free amino acids constitute the largest portion (40%) of the natural moisturizing factor. Their level might decline and cause dry skin condition. The treatment strategy involves the replenishment of these components to the skin, and, to our knowledge, there are no reports that involve dermal delivery of free amino acids. The purpose of the current study was therefore to prepare and characterize different micro-emulsions, micro-emulsion-based hydrogels, and hydrophilic creams loaded with free amino acids for dermal delivery. Oil-in-water microemulsions were prepared using carefully selected formulation components. Poloxamer ® 407 and carbopol ® 934 were used to prepare the hydrogels. All the formulations were characterized for physico-chemical, permeation and cytotoxicity properties. The results showed that the prepared microemulsions had desired droplet size, size distribution, zeta potential, refractive index, and pH. In the gel preparations, the elastic properties prevailed over the viscous behavior. The hydrogels had non-Newtonian shear-thinning behavior with some thixotropic properties. The free amino acids permeated into the deeper layers of the stratum corneum from the microemulsions, and microemulsion-based hydrogels as compared to conventional hydrophilic cream. The hydrogels were more effective than the microemulsions to deliver the FAAs to the desired site of the skin in a sustained manner. Poloxamer-based hydrogel permeated into deeper skin layers than Carbopol-based hydrogel. Formulations prepared using standard free amino acids and those extracted and purified from oyster mushroom had similar characteristics. All the formulations were stable and safe to be applied topically. In conclusion, microemulsions and microemulsion-based hydrogels can be considered as safe carrier systems for dermal delivery of free amino acids.

Texture and mouthfeel are central to the sensory enjoyment of food and beverages. Yet our incomplete understanding of how food boluses are transformed in the mouth limits our texture prediction ability. As well as thin film tribology, the interaction of food colloids with the oral tissue and salivary biofilms plays a key role in texture perception via mechanoreceptors in the papillae. In this study we describe the development of an oral microscope capable of quantitative characterization of the inactions of food colloids with papillae and their concurrent saliva biofilm. We also highlight how the oral microscope revealed key microstructural drivers of several topical phenomena (oral residue formation, coalescence in-mouth, grittiness of protein aggregates and finally microstructural origin of polyphenol astringency) in the domain of texture creation. The coupling of a fluorescent food grade dye with image analysis enabled specific and quantitative determination of the microstructural changes in mouth. Emulsions either underwent no aggregation, small aggregation, or extensive aggregation depending on whether their surface charge facilitated complexation with the saliva biofilm. Quite surprisingly cationic gelatin emulsions that were already aggregated with saliva in mouth underwent coalescence if subsequently exposed to tea polyphenols (EGCG). Large protein aggregates were found to aggregate with the saliva coated papillae, increasing their size tenfold and possibly explaining why there are perceived as gritty. An exciting observation was the oral microstructural changes that occurred upon exposure to tea polyphenols (EGCG). Filiform papillae shrunk, and the saliva biofilm was seen to precipitate/collapse, exposing a very rough tissue surface. These tentative early steps are the first in vivo microstructural insights into the different food oral transformations that are drivers of key texture sensation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This work focuses on developing nanoemulsions using a low-energy emulsification method for the codelivery of donepezil and memantine in one dosage form intended to be administered via the intranasal route for enhanced brain delivery. The nanoemulsion formulation was prepared using a low emulsification technique and characterized using various microscopy and nasal ciliotoxicity studies. The safe nanoemulsion was intended for preclinical pharmacokinetics with brain distribution and pharmacodynamics in a scopolamine-induced murine model. The formulated nanoemulsion was 16 nm in size, with a zeta potential of -7.22 mV, and exhibited a spherical shape. The brain concentration of IN-administered NE for DPZ and MEM was ∼678 and 249 ng/mL after 15 min. This concentration is more than 2 times higher in amount when compared with NE administered via PO, free drug solution administered via IN and PO route both. However, the plasma concentration of IN-administered NE for DPZ and MEM was ∼3 and 28 ng/mL after 15 min. In pharmacodynamic studies, the efficacy of NE administered via the IN route was higher when compared with other groups in neurobehavioral, biochemical estimation, and gene expression studies. The results suggest that the IN route can be explored in the future for the delivery of actives via nanocolloidal carriers in the brain for neurological disorders and can serve as promising alternatives for conventional dosage forms and routes.

Alkaline-extracted walnut protein isolates showed relatively poor solubility and emulsifying properties in many previous studies. However, whether they can be used as potential emulsifiers to stabilize high internal phase emulsions (HIPEs) remains unknown. Herein, walnut protein isolates were prepared by alkaline extraction from walnut kernels with or without pellicles (named PAWPI and AWPI, respectively). PAWPI conjugated with pellicle polyphenols showed improved solubility and higher antioxidant capacity than AWPI. HIPEs were fabricated via a one-step method using AWPI or PAWPI as the sole protein emulsifier. HIPEs (oil fraction of 0.8, with 0.1% β-carotene) could be stabilized by PAWPI at a relatively low concentration of 0.2% (w/v), while at least 1% (w/v) AWPI was required to effectively stabilize HIPEs. HIPEs stabilized by PAWPI had smaller oil droplet sizes than those stabilized by AWPI. Rheological analysis indicated that PAWPI-stabilized HIPEs showed higher viscosity and better viscoelasticity than AWPI-stabilized HIPEs. Large-amplitude oscillation shearing analysis suggested that PAWPI-stabilized HIPEs were stiffer but more brittle than AWPI-stabilized HIPEs. Moreover, both PAWPI- and AWPI-stabilized HIPEs exhibited good storage stability and were relatively stable against heat treatment and ionic strength. PAWPI-stabilized HIPEs showed a higher protective capacity for encapsulated β-carotene than AWPI-stabilized HIPEs. In addition, PAWPI-stabilized HIPEs showed good 3D printability and could be used as a promising edible ink., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I , ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

Introduction: A previous study demonstrated a strong emulsification ability of the culture supernatant obtained by cultivation of Candida albicans in a medium containing a β-1,3-glucan synthesis inhibitor and proposed a novel screening method using emulsification as an indicator for β-1,3-glucan synthesis inhibition (Nerome et al., 2021. Evaluating β-1,3-glucan synthesis inhibition using emulsion formation as an indicator. J Microbiol Methods. 190:106327). The emulsification was presumed to be caused by the proteins released from the cells; however, which proteins have a strong emulsification ability was unclear. Furthermore, as many cell wall proteins are connected to β-1,3-glucan via the carbohydrate moiety of the glycosylphosphatidylinositol (GPI)-anchor, which remains when detached from the cell membrane, emulsification might be detected by inhibiting GPI-anchor synthesis., Objective: This study aimed to confirm whether emulsification could be detected by inhibiting GPI-anchor synthesis and identifying emulsification proteins released by inhibiting the synthesis of GPI-anchor or β-1,3-glucan., Methods: C. albicans was cultured in a medium containing a GPI-anchor synthesis inhibitor, and the emulsification by the culture supernatant was evaluated. We identified cell wall proteins released from the cells upon inhibition of β-1,3-glucan or GPI-anchor synthesis by mass spectrometry, their recombinant proteins were prepared, and their emulsification efficacy was evaluated., Results: In GPI-anchor synthesis inhibition, a weak emulsification phenomenon was observed compared to the β-1,3-glucan synthesis inhibition. Phr2 protein was released from the cells upon GPI-anchor synthesis inhibition, and recombinant Phr2 showed a strong emulsification activity. Phr2 and Fba1 proteins were released upon β-1,3-glucan synthesis inhibition, and recombinant Fba1 showed a strong emulsification activity., Conclusions: We concluded that the emulsion phenomenon could be used to screen β-1,3-glucan and GPI-anchor synthesis inhibitors. Also, the two kinds of inhibitors could be distinguished by differences in the growth recovery by osmotic support and strength of emulsification. In addition, we identified the proteins involved in emulsification., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/function relationships. This work aimed to attest the use of extracted BSY mannoproteins as a clean label and vegan source of ingredients for the replacement of food additives and protein from animal sources. To achieve this, structure/function relationships were performed by isolating polysaccharides with distinct structural features from BSY, either by using alkaline extraction (mild treatment) or subcritical water extraction (SWE) using microwave technology (hard treatment), and assessment of their emulsifying properties. Alkaline extractions solubilized mostly highly branched mannoproteins ( N -linked type; 75%) and glycogen (25%), while SWE solubilized mannoproteins with short mannan chains ( O -linked type; 55%) and (1→4)- and (β1→3)-linked glucans, 33 and 12%, respectively. Extracts with high protein content yielded the most stable emulsions obtained by hand shaking, while the extracts composed of short chain mannans and β-glucans yielded the best emulsions by using ultraturrax stirring. β-Glucans and O -linked mannoproteins were found to contribute to emulsion stability by preventing Ostwald ripening. When applied in mayonnaise model emulsions, BSY extracts presented higher stability and yet similar texture properties as the reference emulsifiers. When used in a mayonnaise formulation, the BSY extracts were also able to replace egg yolk and modified starch (E1422) at 1/3 of their concentration. This shows that BSY alkali soluble mannoproteins and subcritical water extracted β-glucans can be used as replacers of animal protein and additives in sauces.

Pickering emulsions are free from molecular and classical surfactants and are stabilized by solid particles, creating long-term stability against emulsion coalescence. Additionally, these emulsions are both environmentally and skin-friendly, creating new and unexplored sensorial perceptions. Although the literature mostly describes conventional emulsions (oil-in-water), there are unconventional emulsions (multiple, oil-in-oil and water-in-water) with excellent prospects and challenges in skin application as oil-free systems, permeation enhancers and topical drug delivery agents, with various possibilities in pharmaceutical and cosmetic products. However, up to now, these conventional and unconventional Pickering emulsions are not yet available as commercial products. This review brings to the discussion some important aspects such as the use of phases, particles, rheological and sensorial perception, as well as current trends in the development of these emulsions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study sought to improve the biological fate of β-carotene obtained from spinach, using in vitro digestion, in situ single-pass intestinal perfusion, and in vivo approaches, to investigate the effects of excipient emulsions with medium- (MCT) and long-chain triglyceride (LCT) as a vehicle for improved health benefits of β-carotene. Results showed that the bioavailability and bioactivity of β-carotene were both significantly higher in the excipient emulsions relative to those without the emulsions. This was especially true when LCT was used as the vehicle. These results were confirmed by bioaccessibility, duodenal absorption, and in vivo absorption and metabolism. Furthermore, animal feeding studies revealed that LCT may have the potential to promote triglyceride and apo-B48 reconstitution and secretion. This suggested that LCT may facilitate the entry of carotenoids into circulation via the lymphatic pathway. These results highlight the importance of the optimization of excipient foods to improve the efficacy of lipophilic carotenoid., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An emulsion delivery system may be affected significantly by oil phase composition in terms of digestion behavior and bioavailability of the delivered substance. In this study, emulsions loaded with cannabidiol (CBD) were prepared with medium chain triglyceride (MCT), long chain triglyceride (LCT) or MCT/LCT(1:1) as carrier oil and whey protein-maltodextrin conjugate as emulsifier, and the digestion behavior of emulsion and bioavailability of CBD were assessed in vitro and in vivo. The particle size of emulsions throughout the in vitro digestion process was in the order of MCT < MCT/LCT < LCT, and three emulsions showed consistent particle size changes: stable in oral phase, sharply increased in gastric phase, and decreased in small intestine. After intestinal digestion, about 90% of free fatty acids (FFA) was released in MCT emulsion, followed by MCT/LCT (76%) and then LCT (45%). CBD was degraded during gastrointestinal digestion and the transformation stability of CBD in oil phase was in the order of LCT > MCT/LCT > MCT. Although CBD had higher bioaccessibility in MCT and MCT/LCT emulsions, the bioavailability of CBD in LCT was the highest (43%), followed by MCT/LCT (39%), MCT (33%). In vivo pharmacokinetic study showed that MCT/LCT and LCT were more favorable for CBD transport and absorption. The results may provide useful information for the construction of delivery systems, protecting CBD molecules, and improving their bioavailability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, tomato seed oil conventional emulsion (7 μm) and nanoemulsion (0.146 µm) with desirable stability were prepared, then the effect of tomato seed oil addition (bulk and emulsified forms) and thermal treatment on properties of tomato juice was evaluated. Tomato juice without oil and heat treatment exhibited the lowest bioaccessibility of lycopene (17.8 %). Incorporation of oil and applying heat treatment significantly increased the extent of lipid digestion and bioaccessibility of lycopene. In this regard, the nanoemulsion had the highest bioaccessibility (44.85 %) compared to conventional emulsion (33.90 %) and bulk oil (27.11 %), due to the smaller oil droplets. The oxidative stability of oil in heat-treated tomato juice samples decreased during 28 days of storage at 4 °C, whereas the nanoemulsion exhibited the highest peroxide value (4.43 meq O 2 /kg of oil) compared to conventional emulsion and bulk oil (3.91 and 3.49 meq O 2 /kg of oil, respectively) at the end of the period., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Here, we developed a microfluidic-assisted blood-brain barrier (BBB) device and tested the effects of omega-3 fatty acids on neuroimmune interactions after orthopaedic surgery., Methods: A microfluidic-assisted BBB device was established using primary human cells. Tight junction proteins, vascular cell adhesion molecule 1 (VCAM-1), BBB permeability, and astrocytic networks were assessed after stimulation with interleukin (IL)-1β and in the presence or absence of a clinically available omega-3 fatty acid emulsion (Omegaven®; Fresenius Kabi, Bad Homburg, Germany). Mice were treated 1 h before orthopaedic surgery with 10 μl g -1 body weight of omega-3 fatty acid emulsion i.v. or equal volumes of saline. Changes in pericytes, perivascular macrophages, BBB opening, microglial activation, and inattention were evaluated., Results: Omega-3 fatty acids protected barrier permeability, endothelial tight junctions, and VCAM-1 after exposure to IL-1β in the BBB model. In vivo studies confirmed that omega-3 fatty acid treatment inhibited surgery-induced BBB impairment, microglial activation, and delirium-like behaviour. We identified a novel role for pericyte loss and perivascular macrophage activation in mice after surgery, which were rescued by prophylaxis with i.v. omega-3 fatty acids., Conclusions: We present a new approach to study neuroimmune interactions relevant to perioperative recovery using a microphysiological BBB platform. Changes in barrier function, including dysregulation of pericytes and perivascular macrophages, provide new targets to reduce postoperative delirium., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the safety and efficacy of resveratrol microemulsion gel in improving pigmentation., Methods: Resveratrol microemulsion gel was prepared by the microemulsion solubilization method, and its quality was evaluated. The transdermal and drug retention rates of resveratrol in vivo were assessed using a transdermal test. The inhibitory effects of resveratrol suspension and microemulsion on tyrosinase activity and melanin production of A375 human melanocytes and zebrafish embryos were compared. A skin patch test was used to investigate the safety of the gel on 15 volunteers., Results: The microemulsion gel was homogeneous and stable. Compared with suspension and microemulsion, the drug penetration rate and skin retention in the microemulsion gel group were significantly increased. Compared with the suspension group, the activity of melanocyte tyrosinase in A375 human melanocyte was significantly inhibited in the microemulsion group, and the melanin production rate of A375 human melanocyte and the melanin area of zebrafish yolk was decreased. All 15 volunteers tested negative for the human skin patch., Conclusions: The microemulsion gel could significantly enhance the ability of resveratrol to inhibit the formation of melanin without causing side effects. These data provide the experimental basis for developing and applying the preparation for improving pigmentation.

Background: Wilms' tumor 1 (WT1) is highly expressed in various solid tumors and hematologic malignancies. DSP-7888 (adegramotide/nelatimotide) Emulsion is an investigational therapeutic cancer vaccine comprising three synthetic epitopes derived from WT1. We evaluated the mechanism of action of DSP-7888 Emulsion, which is hypothesized to induce WT1-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs)., Methods: The ability of nelatimotide and adegramotide to induce WT1-specific CD8 + T cells and CD4 + T cells was assessed in human peripheral blood mononuclear cells (PBMCs). The ability of DSP-7888 Emulsion to induce WT1-specific CTLs in vivo was assessed using human leukocyte antigen-I (HLA-I) transgenic mice. To assess how adegramotide, the helper peptide in DSP-7888 Emulsion, enhances WT1-specific CTLs, HLA-I transgenic mice were administered DSP-7888 or nelatimotide-only Emulsion. Interferon-gamma secretion under antigen stimulation by splenocytes co-cultured with or without tumor cells was then quantified. The effects of combination treatment with DSP-7888 Emulsion and an anti-programmed cell death protein 1 (PD-1) antibody on tumor volume and the frequency of tumor-infiltrating WT1-specific T cells were assessed in HLA-I transgenic mice implanted with WT1 antigen-positive tumors., Results: The peptides in DSP-7888 Emulsion were shown to induce WT1-specific CTLs and HTLs in both human PBMCs and HLA-I transgenic mice. Unlike splenocytes from nelatimotide-only Emulsion-treated mice, splenocytes from DSP-7888 Emulsion-treated mice exhibited high levels of interferon-gamma secretion, including when co-cultured with tumor cells; interferon-gamma secretion was further enhanced by concomitant treatment with anti-PD-1. HLA-I transgenic mice administered DSP-7888 Emulsion plus anti-PD-1 experienced significantly greater reductions in tumor size than mice treated with either agent alone. This reduction in tumor volume was accompanied by increased numbers of tumor-infiltrating WT1-specific CTLs., Conclusions: DSP-7888 Emulsion can promote both cytotoxic and helper T-cell-mediated immune responses against WT1-positive tumors. Adegramotide enhances CTL numbers, and the CTLs induced by treatment with both nelatimotide and adegramotide are capable of functioning within the immunosuppressive tumor microenvironment. The ability of anti-PD-1 to enhance the antitumor activity of DSP-7888 Emulsion in mice implanted with WT1-positive tumors suggests the potential for synergy., (© 2022. The Author(s).)

Whey protein hydrolysate (WPH), maltodextrin (MD), low methoxy pectin (LMP) and high methoxy pectin (HMP) were used to study the interface binding under high temperature sterilization conditions (121 °C, 15 min). The effect of competitive binding of MD and pectin with interface protein on the storage stability and gastrointestinal fate of fish oil emulsion was studied. The low-molecular-weight MD and the interface protein undergo a wide range of covalent binding through the Maillard reaction, while a small amount of high-molecular-weight pectin can form a protective shell with the interface protein through electrostatic interaction to inhibit the covalent reaction of MD, which was called competitive binding. However, due to the bridging and depletion flocculation of pectin, the emulsification stability of fish oil emulsion reduced. After 13 days of storage, compared with the particle size of the WPH fish oil emulsion (459.18 nm), the fish oil emulsion added with LMP and HMP reached 693.58 nm and 838.54 nm, respectively. In vitro digestion proved that WPH fish oil emulsion flocculated rapidly in the stomach (1.76 μm), while WPH-MD and WPH-MD-pectin fish oil emulsions flocculated slightly (less than800 nm). WPH-MD-pectin delayed digestion in the gastrointestinal tract, and HMP exhibited a better slow-release effect. This study provides reference for the design of multi-component functional drinks and other bioactive ingredient delivery system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a severe threat to human health. Polygonum multiflorum (PM) has been proven to remedy mitochondria and relieve MAFLD, but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear., Aim: To research the active ingredients of PM adjusting mitochondria to relieve high-fat diet (HFD)-induced MAFLD in rats., Methods: Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms. The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry (mitochondrial pharmacochemistry). The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model, respectively., Results: PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the liver mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated., Conclusion: PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD. Thus, PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction. Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Formulation of curcumin in a microemulsion with a high loading capacity and that favors its penetration into the skin., Significance: Take advantage of the properties of microemulsions to promote the penetration of curcumin into the skin, with the aim of enhancing its therapeutic effects., Methods: Curcumin was formulated in microemulsions based on oleic acid (oil phase), Tween® 80 (surfactant), and Transcutol ® HP (cosurfactant). The microemulsion formation area was mapped by constructing pseudo-ternary diagrams for surfactant:co-surfactant ratios 1:1, 1:2, and 2:1. Microemulsions were characterized through measurements of specific weight, refractive index, conductivity, viscosity, droplet size, and in vitro skin permeation studies., Results: Nine microemulsions were prepared and characterized, showing clear, stable formulations with globule size dependent on the proportion of the components. The microemulsion with the highest loading capacity (60 mg/mL), based on Tween ® 80, Transcutol ® HP, oleic acid, and water (40:40:10:10) was able to penetrate the viable epidermis, finding a total amount of curcumin in the receptor medium at 24 h of 10.17 ± 9.7 µg/cm 2 . The distribution of curcumin in the skin, visualized by confocal laser scanning microscopy, showed that the maximum amount was located between 20 and 30 µm., Conclusion: The inclusion of curcumin in a microemulsion allows its passage into and through the skin. The localization of curcumin, especially in the viable epidermis, would be important for those cases where local conditions are sought to be treated.

In this study, a natural antioxidant emulsifier, Millettia speciosa Champ polysaccharide conjugates (MSC-PC), was used for fabricating oil-in-water emulsion, and the influences of MSC-PC on β-carotene stability and bioaccessibility were studied. Results suggested that MSC-PC stabilized emulsion exhibited excellent resistance to a wide range of salt levels (0-500 mM of Na + ), thermal treatments (50-90 °C) and pH values (3.0-11.0). MSC-PC also exhibited an outstanding inhibition capacity on lipid oxidation. Besides, MSC-PC stabilized emulsion had a better protective effect on β-carotene than other systems. Interestingly, in spite of similar lipolysis extent, β-carotene bioaccessibility in MSC-PC fabricated emulsion (14.75 %) was markedly higher than that in commercial Tween 80 fabricated emulsion (10.08 %), likely due to the steric-hindrance effect and antioxidant ability of MSC-PC, building interfacial layers that prevented β-carotene from degradation. This work supplied a deep insight into elucidating the mechanisms of emulsifying performance and β-carotene protection effect of MSC-PC fabricated emulsion., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The biodegradation of rubber materials is considered as a sustainable recycling alternative, highlighting the use of microorganisms and enzymes in oxidative processes of natural rubber. Currently, the main challenge is the treatment of rubber materials such as waste tyres, where the mixture of rubber polymers with different additives and the cross-linked structure obtained due to the vulcanisation process positions them as highly persistent materials. This study characterises the degradation of different rubber-containing substrates in in vivo and in vitro processes using the bacterium Rhodococcus rhodochrous and the oxygenase latex clearing protein (Lcp) from the same strain. For the first time, the degradation of polyisoprene particles in liquid cultures of R. rhodochrous was analysed, obtaining up to 19.32% mass loss of the polymer when using it as the only carbon source. Scanning electron microscopy analysis demonstrated surface alteration of pure polyisoprene and vulcanised rubber particles after 2 weeks of incubation. The enzyme Lcp RR was produced in bioreactors under rhamnose induction and its activity characterised in oxygen consumption assays at different enzyme concentrations. A maximum consumption of 28.38 µmol O2 /min was obtained by adding 100 µg/mL Lcp RR to a 2% (v/v) latex emulsion as substrate. The bioconversion of natural rubber into reaction degradation products or oligoisoprenoids was calculated to be 32.54%. Furthermore, the mass distribution of the oligoisoprenoids was analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and 17 degradation products, ranging from C20 to C100 oligoisoprenoids, were identified. The multi-enzymatic degradation capacity of R. rhodochrous positions it as a model microorganism in complex degradation processes such as in the case of tyre waste., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Retinoic acid (RA) is an approved treatment for skin photoaging induced by ultraviolet (UVA). Topically applied RA is mainly located in the stratum corneum (SC) with limited diffusion into the deeper strata. A delivery system capable of facilitating dermal delivery and cellular internalization for RA is critical for a successful photoaging therapy. Two delivery approaches, namely nanoparticles and laser ablation, were combined to improve RA's absorption efficacy and safety. The nanoparticle absorption enhancement by the lasers was compared between full-ablative (Er:YAG) and fractional (CO 2 ) modalities. We fabricated poly-L-lactic acid (PLA) and PLA/poly(lactic-co-glycolic acid) (PLGA) nanoparticles by an emulsion-solvent evaporation technique. The mean size of PLA and PLA/PLGA nanocarriers was 237 and 222 nm, respectively. The RA encapsulation percentage in both nanosystems was > 96 %. PLA and PLA/PLGA nanocarriers promoted RA skin deposition by 5- and 3-fold compared to free control. The ablative lasers further enhanced the skin deposition of RA-loaded nanoparticles, with the full-ablative laser showing greater permeation enhancement than the fractional mode. The skin biodistribution assay evaluated by confocal and fluorescence microscopies demonstrated that the laser-assisted nanoparticle delivery achieved a significant dermis and follicular accumulation. The cell-based study indicated a facile uptake of the nanoparticles into the human dermal fibroblasts. The nanoparticulate RA increased type I collagen and elastin production in the UVA-treated fibroblasts. A reduction of matrix metalloproteinase (MMP)-1 was also highlighted in the photoaging cells. The calculation of therapeutic index (TI) by multiplying collagen/elastin elevation percentage and skin deposition predicted better anti-photoaging performance in Er:YAG laser-assisted nanoparticle delivery than CO 2 laser. Nanoencapsulation of RA decreased the cytotoxicity against skin fibroblasts. In vivo skin tolerance test on a nude mouse showed less skin damage after topical application of the nanoparticles than free RA. Our results hypothesized that the laser-mediated nanoparticle delivery provided an efficient and safe use for treating photoaging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Because ceramide-like lipo-amino acid cholesteryl derivatives can exert a bound water-holding function due to their lamellae-forming properties, in this study, we determined if topical application of those derivatives to atopic dry skin would elicit an ameliorative effect on skin symptoms, at least on its water-holding function. In this clinical study, daily treatment with a nano-emulsion containing 10% phytosteryl/octyldodecyl lauroyl glutamate (POLG) significantly (p < 0.0001) improved skin symptoms, including dryness/scaling, itchiness and stimulus sensations, in the non-lesional skin of patients with atopic dermatitis (AD) at 3 and at 6 weeks compared with week 0. Those significant improvements in skin symptoms were accompanied by a significantly enhanced water content (conductance) and a significant improvement of roughness (SESC) and smoothness (SESM) values measured using a Visioscan at 3 and 6 weeks. Those effects appeared concomitant with a significantly increased corneocyte size, a significantly down-regulated degree of thick abrasions, and a significant impairment of the corneocyte lipid envelope at 6 weeks. Thus, our clinical study suggests, for the first time, that topical application of the POLG nano-emulsion has the distinct potential to ameliorate atopic dry skin symptoms, particularly scaling and itchiness, in the skin of patients with AD. Those effects result from alleviation of the disrupted water-holding function probably due to the increased supply of lamellae structures into the stratum corneum despite the failure to improve barrier function.

Polymeric nanocarriers (NCs) are efficient vehicles to prevent drug unspecific biodistribution and increase the drug amounts delivered to tumor tissues. However, some toxicological aspects of NCs still lack a comprehensive assessment, such as their effects on cellular processes that lead to toxicity. We evaluate the interaction of poly(lactic- co -glycolic acid) (PLGA) NCs prepared using dextran (Dex) and Pluronic®-F127 as stabilizing agents with myocardial cells (H9C2), breast adenocarcinoma cells (MCF-7) and macrophages (RAW 264.7) to address the effect of Dex in PLGA NC formulations. By an emulsion diffusion method, doxorubicin-loaded NCs were prepared with no Dex (PLGA-DOX), 1% (w/v) Dex (Dex1/PLGA-DOX) and 5% (w/v) Dex (Dex5/PLGA-DOX). Uptake analyses revealed a significant reduction in Dex5/PLGA-DOX NC uptake by H9C2 and MCF-7, as in the case of Dex1/PLGA-DOX NCs in the absence of in vitro protein corona, revealing an effect of dextran concentration on the formation of protein corona. RAW 264.7 cells presented a greater uptake of Dex5/PLGA-DOX NCs than the other NCs likely because of receptor mediated endocytosis, since C-type lectins like SIGN-R1, mannose receptors and scavenger receptor type 1 that are expressed in RAW 264.7 can mediate Dex uptake. Despite the lower uptake, Dex5/PLGA-DOX NCs promote the generation of reactive oxygen species and oxidative membrane damage in MCF-7 and H9C2 even though cellular metabolic activity assessed by MTT was comparable among all the NCs. Our results highlight the importance of an in-depth investigation of the NC-cell interaction considering additional mechanisms of damage apart from metabolic variations, as nanoparticle-induced damage is not limited to imbalance in metabolic processes, but also associated with other mechanisms, e.g. , membrane and DNA damage.

Non-typhoidal Salmonella serotypes are well adapted to utilize the inflammation for colonization in the mammalian gut mucosa and cause loss of the integrity of the epithelial barrier in the mammalian intestine. The present study assessed the protective efficacy of fish oil-in-water nanoemulsion, compared to the conventional emulsion, towards the intestinal epithelial barrier against invasive infection of Salmonella enterica serovar Typhimurium strain SL1344 in an in vivo streptomycin-treated mouse model. Non-typhoidal Salmonella enterica serovar Typhimurium strain SL1344 expresses its invasiveness by creating extreme inflammatory assault in the mammalian host lumen via its repertoire of secretory or membrane-bound proteins. Prophylactic treatment of ω-3 polyunsaturated fatty acid-rich fish oil nanoemulsion not only reduced the inflammatory markers by 4-5 fold against the established infection but also retained the gut barrier efficiency as shown by FITC-dextran permeability assay. Though the conventional emulsion also showed similar trends, the efficacy was significantly better with nanoemulsion treatment but neither the nanoemulsion nor conventional emulsion caused any significant change in the microbial colonization of the murine gut mucosa. Mechanistic assessment of the nanoemulsion against inflammation and invasion across the Caco-2 cell monolayer revealed that nanoemulsion treatment protected the expression of Zona occludens-1 along the tight junction, almost by 3-fold as compared to the infected cell monolayer. Such protection was evinced by the trans-epithelial electrical resistance value and the FITC-dextran permeability analysis as well. Fish oil nanoemulsion treatment has also shown significant reduction in pro-inflammatory cytokine expression by the Salmonella strain SL1344 infected Caco-2 cell monolayer. Conventional emulsion also showed distinct protection, but the nanoemulsion offered better protection at the same dosage of fish oil, probably due to its better bioavailability. The results proved that fish oil-loaded nanoemulsion can be efficacious towards maintaining the barrier function and protecting against systemic bacteremia during invasive intestinal infection.

Purpose: The aim of this study is to convert tretinoin (Tr), an active pharmaceutical ingredient (API), into ionic liquid for improving aqueous solubility and permeability of Tr in transdermal drug delivery applications., Methods: Three ionic liquids of Tr (TrILs) were synthesized through neutralization reactions, which were characterized to confirm the compositions and ionic interactions. The in vitro drug release studies and skin penetration tests were carried out to assess the performance of formulations containing TrILs., Results: The TrIL formed by choline and Tr at the molar ratio of 2:1 (2[Ch][Tr]), was found to have prominent solubility, stability as well as permeability. In contrast with the insoluble Tr, 2[Ch][Tr] presented as clear and transparent aqueous solution even after diluted to 14%. The aqueous solution of 2[Ch][Tr] demonstrated better permeation effect, of which the solution with 20% of 2[Ch][Tr] showed the optimal delivery efficiency in both epidermis (2.09 ± 0.18‰) and dermis (3.31 ± 0.48‰), realizing the improvement on the permeability of API. Meanwhile, TrILs can be easily fabricated as o/w emulsions as transdermal formulation. The emulsions are also able to improve the skin permeability of Tr, though the enhanced effect is inferior to TrILs solutions., Conclusions: Ionic liquid technology can be used to improve solubility and permeability of Tr, providing a high potential strategy for the development of topical formulations and the desired transdermal application of drugs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated the influence of carrier oils on the in vitro and in vivo bioavailability of PTE encapsulated in scallop gonad protein isolates (SGPIs)-epigallocatechin gallate (EGCG) conjugate stabilized emulsions. The SGPIs-EGCG stabilized emulsions were subjected to an in vitro simulated digestion, and the resulting corn oil and MCT micelles were used to evaluate the PTE transportation using the Caco-2 cell model. Both emulsions remarkably improved the bioaccessibility of PTE in the micelle phase. Nevertheless, corn oil emulsions increased trans-enterocyte transportation of PTE more efficiently than MCT emulsions. Furthermore, the maximum plasma concentrations of PTE and its metabolites in mice fed with PTE emulsions were prominently higher than those in mice fed with PTE solution, while the in vivo metabolic patterns of PTE in different oil-stabilized emulsions were different. Therefore, SGPIs-EGCG stabilized emulsions could enhance the bioavailability of PTE through controlled release, in which corn oil is more suitable than MCT.

To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.

A key event at the onset of development is the activation of a contractile actomyosin cortex during the oocyte-to-embryo transition 1-3 . Here we report on the discovery that, in Caenorhabditis elegans oocytes, actomyosin cortex activation is supported by the emergence of thousands of short-lived protein condensates rich in F-actin, N-WASP and the ARP2/3 complex 4-8 that form an active micro-emulsion. A phase portrait analysis of the dynamics of individual cortical condensates reveals that condensates initially grow and then transition to disassembly before dissolving completely. We find that, in contrast to condensate growth through diffusion 9 , the growth dynamics of cortical condensates are chemically driven. Notably, the associated chemical reactions obey mass action kinetics that govern both composition and size. We suggest that the resultant condensate dynamic instability 10 suppresses coarsening of the active micro-emulsion 11 , ensures reaction kinetics that are independent of condensate size and prevents runaway F-actin nucleation during the formation of the first cortical actin meshwork., (© 2022. The Author(s).)

Background: The role of hepatoportal glucose sensors is poorly understood in the context of insulin resistance., Objectives: We assessed the effects of glucose infusion in the portal vein on insulin tolerance in 2 rat models of insulin resistance, and the role of capsaicin sensitive nerves in this signal., Methods: Male Wistar rats, 8 weeks old, weighing 250-275 g, were used. Insulin and glucose tolerance were assessed following a 4-hour infusion of either glucose or saline through catheterization in the portal vein in 3 paradigms. In experiment 1, for diet-induced insulin resistance, rats were fed either a control diet (energy content: proteins = 22.5%, carbohydrates = 64.1%, and lipids = 13.4%) or a high-fat diet (energy content: proteins = 15.3%, carbohydrates = 40.3%, and lipids =44.4%) for 4 months. In experiment 2, for centrally induced peripheral insulin resistance, catheters were inserted in the carotid artery to deliver either an emulsion of triglycerides [intralipid (IL)] or saline towards the brain for 24 hours. In experiment 3, for testing the role of capsaicin-sensitive nerves, experiment 2 was repeated following a periportal treatment with capsaicin or vehicle., Results: In experiment 1, when compared to rats fed the control diet, rats fed the high-fat diet exhibited decreased insulin and glucose tolerance (P ≤ 0.05) that was restored with a glucose infusion in the portal vein (P ≤ 0.05). In experiment 2, infusion of a triglyceride emulsion towards the brain (IL rats) decreased insulin and glucose tolerance and increased hepatic endogenous production when compared to saline-infused rats (P ≤ 0.05). Glucose infusion in the portal vein in IL rats restored insulin and glucose tolerance, as well as hepatic glucose production, to controls levels (P ≤ 0.05). In experiment 3, portal infusion of glucose did not increase insulin tolerance in IL rats that received a periportal pretreatment with capsaicin., Conclusions: Stimulation of hepatoportal glucose sensors increases insulin tolerance in rat models of insulin resistance and requires the presence of capsaicin-sensitive nerves., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

This study aimed to elucidate the impacts of carrier oil types (long chain triglycerides (LCT), medium chain triglycerides (MCT), and orange oil (indigestible oil)) on the micellization and cellular uptake of β-carotene (BC) formulated in O/W emulsions, with an emphasis on the role of intestinal transporters. The micellization and cellular uptake of BC in the gastrointestinal tract were evaluated via an in vitro digestion model and a Caco-2 cell monolayer. And the interactions between lipids and intestinal transporters were monitored by nontargeted lipidomics, RT-PCR, and Western blot. The BC micellization rates followed a decreasing trend in emulsions: corn oil (69.47 ± 4.19%) > MCT (22.22 ± 0.89%) > orange oil (11.01 ± 2.86%), whereas the cellular uptake rate of BC was significantly higher in MCT emulsion (56.30 ± 20.13%) than in corn oil emulsion (14.01 ± 1.04%, p < 0.05). The knockdown of SR-B1 led to a 31.63% loss of BC cellular uptake from MCT micelles but had no effect on corn oil micelles. Lipidomics and transporter analysis revealed that TG (10:0/10:0/12:0) and TG (10:0/12:0/12:0) might be the fingerprint lipids that promoted the cellular absorption of BC-MCT micelles via stimulating the mRNA expression of SR-B1 .

Lipophilic nutrients are known to have relatively poor absorption, thus limiting their bioaccessibility. Consequently, researchers in food and pharmaceutical areas are exploring different techniques to promote the efficient delivery of lipophilic nutrients. The effects of two polar lipids, namely mono-, di-glycerides (MDG) and lecithin (PL), on the bioaccessibility of lipophilic nutrients were investigated in this study with a protein-based emulsion model system. During the emulsion preparation and formation, the incorporation of MDG/PL was found to benefit the dissolution and stabilization of lipophilic nutrients, such as lutein, and could also modify the construction of the emulsion surface. An in vitro digestion study showed that the use of MDG/PL could significantly increase the bioaccessibility of lipophilic nutrients [lutein, vitamin E, and docosahexaenoic acid (DHA)] by 13.52%, 186.90%, and 36.17% in a protein-based emulsion system. The use of MDG and PL decreased the interfacial tension in all the samples: protein only 20.65 mN m -1 , protein-PL 6.47 mN m -1 , and protein-MDG/PL 4.23 mN m -1 , as well as 12.11 mN m -1 , 1.26 mN m -1 and 1.16 mN m -1 with the presence of bile salts. Caco-2 cell culture results showed that, with the application of MDG/PL, the absorption rate of micelles was higher than that in the other groups and this resulted in a 70% absorption increase for lutein. Therefore, MDG/PL can improve the lipophilic nutrient absorption via promoting the affinity of formed micelles to the enterocytes of the small intestine. This study exhibited the effectiveness of MDG/PL on improving the bioaccessibility of lipophilic nutrients in a protein-based emulsion system mimicking the digestion and absorption fate of breast milk in an infant's gastric intestinal tract, thus suggesting that MDG/PL can be used as a technical pathway to improve the absorption of lipophilic nutrients.

Although conjugated linoleic acid (CLA) has various excellent physiological functions, it exhibits poor water solubility and high oxidation sensitivity, which limits its applications in food industry. To solve this problem, a stable oil in water emulsion was used for protecting CLA. In this study, glycosylated whey protein isolate (GWPI) formed by whey protein isolate (WPI) and galactose was used to produce CLA emulsion, and then its physicochemical stabilities, gastrointestinal behaviors were evaluated. The results showed that creaming index, primary oxidation products and secondary oxidation products of GWPI-stabilized emulsion at reaction time of 4 h (GWPI-4 h) decreased by 32.43%, 95.98% and 87.34% when stored for 15 days, compared with WPI-loaded CLA emulsion. Additionally, GWPI promoted lipid digestion and led to an improvement of stability and gastrointestinal fate of GWPI-stabilized CLA emulsion. These findings confirmed that GWPI established an emulsification-based delivery system for protecting CLA to exert its physiological functions., (Copyright © 2022. Published by Elsevier Ltd.)

The main objective of this research was to develop a self-emulsified nanoemulsion (SEN) dosage form of insulin where insulin is loaded into the lipid phase of the nanoemulsion for enhanced absorption through intranasal delivery. When loaded into the lipid droplets (oil phase), insulin can be protected from enzymatic degradation, can penetrate through the mucus gel barrier in a comparatively effective manner and can be absorbed through transcellular permeation along with paracellular route. To incorporate lipophilicity to insulin molecule, Ins-SPC (Soy-L-α-phosphatidylcholine) complex was prepared by solid dispersion method to load insulin into the oil phase. The cytotoxicity of SPC and the developed nanoemulsions was tested on the human nasal epithelial cells in vitro. An optimized formulation with high loading of insulin and low in vitro cytotoxicity was developed and characterized. To predict the absorption of insulin through nasal mucosa in vivo by the nanoemulsion system, the insulin-loaded SEN along with controls was tested for the transport through human nasal epithelial cell monolayer in vitro. The insulin-loaded SEN significantly (p < 0.01) enhanced the permeation of insulin by three times as compared to the insulin solution. The in vivo absorption of insulin after intranasal delivery of the insulin-loaded SEN was evaluated in anesthetized rats. The results show that the C max (maximum plasma concentration) and the bioavailability (relative to the subcutaneous delivery) of the insulin-loaded SEN was 255.9 µU/ml and 68 %, respectively, while the intranasal delivery of the insulin solution resulted in only 5.8 µU/ml of C max and 5% of relative bioavailability. Intranasal delivery of 3.6 IU/kg insulin-loaded SEN decreased the plasma glucose level remarkably, achieving a maximum reduction of 70%, and the glucose reduction activity lasted for the whole experimental period of 4 h. Histological examination of the nasal mucosa showed no apparent signs of toxicity at the site of administration after single dose of the insulin-loaded SEN. These results demonstrate that the insulin-loaded SEN significantly enhanced insulin absorption through intranasal delivery, indicating that the developed nanoemulsion system offers a favorable approach for intranasal delivery of insulin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This research aimed to induce repulsive gelation in Citrem-stabilized O/W emulsions by creating a secondary layer of chitosan around the droplets. A range of chitosan concentrations (0-0.25 wt%) and degrees of deacetylation (DDA 50% and 93%) were used to establish the conditions for repulsive gelation in 36 wt% O/W emulsion. The bilayer emulsions were prepared by the electrostatic deposition of positively charged chitosan on negatively charged Citrem-stabilized droplets at pH 4. The droplet size increased from <0.5 μm for the primary emulsion to 5-10 μm at an intermediate chitosan concentration (0.05-0.15 wt%) due to bridging flocculation and again dropped to 1.7-3.6 μm at higher concentrations (0.2 and 0.25 wt%). The droplet charge changed from -48 mV for the primary emulsion to +41.4 and +54.5 mV after surface saturation by DDA 50 and DDA 93 chitosan, respectively. The strain and frequency-dependent rheology indicated that with an increase in the chitosan concentration, emulsions changed from a viscoelastic liquid for monolayer emulsions to strong attractive gel due to bridging flocculation at an intermediate chitosan concentration. At a higher concentration, repulsive gels were formed at complete coverage due to an increase in the effective oil volume fraction towards close packing resulting from the expansion of the interfacial steric barrier and charge cloud thickness. The overall lipid digestibility during in vitro digestion was 25.7% for monolayer emulsions, which decreased with increased chitosan concentration and reached the lowest at surface saturation (17.5%). It was proposed that the formation of the Citrem-chitosan bilayer controlled lipid digestibility by delaying the action of gastric and pancreatic lipases. Such bilayer emulsion gels can be utilized for structure formation in reduced-fat foods.

Microemulsions are transparent, thermodynamically stable colloidal systems. Over the recent years, they have been increasingly investigated due to their potential as skin delivery vehicles for a wide range of drug molecules. The nanoscale particle size and the specificity of microemulsion components are the main features determining the skin permeation process. However, in order to effectively cross the skin barrier, the active substance itself should also meet a number of requirements, such as relatively small molecular weight, high lipophilicity with certain polarity as well as a specific partition coefficient. This review focuses on recent advancements in topical microemulsion systems related to the transport of active ingredients into the skin, including those with high molecular weight and high polarity. Selected studies have shown that permeation of therapeutic macromolecules can be increased by the correct (i.e. tailored to a specific drug) design of the microemulsion. The degree of skin penetration as well as the kinetics and the site of drug release can be controlled by appropriate qualitative and quantitative selections of penetration promoters (microemulsion components), the structure of microemulsion and its viscosity. The drug-carrier interactions can also affect the effectiveness of microemulsion formulation. These relations have been described and evaluated in this review article., (Copyright © 2022 Elsevier B.V. All rights reserved.)