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Background/Objectives: This study aimed to develop gastroretentive tablets based on mucoadhesive–floating systems with encapsulated gentian (Gentiana lutea, Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Methods: Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). Results: The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Conclusions: Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation. [ABSTRACT FROM AUTHOR]

Background and objectives: The use of polymeric nanoparticles (NPs) in drug delivery systems offers the advantages of enhancing drug efficacy and minimizing side effects; Methods: In this study, L-threonine polyurethane (LTPU) NPs have been fabricated by water-in-oil-in-water emulsion and solvent evaporation using biodegradable and biocompatible LTPU. This polymer was pre-synthesized through the use of an amino acid-based chain extender, desaminotyrosyl L-threonine hexyl ester (DLTHE), where urethane bonds are formed by poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) triblock copolymer and 1,6-hexamethylene diisocyanate (HDI). LTPU is designed to be degraded by hydrolysis and enzymatic activity due to the presence of ester bonds and peptide bonds within the polymer backbone. LTPU NPs were fabricated by water-in-oil-in-water double emulsion solvent evaporation methods; Results: The polymerization of LTPU was confirmed by 1H-NMR, 13C-NMR, and FT-IR spectroscopies. The molecular weights and polydispersity, determined with GPC, were 28,800 g/mol and 1.46, respectively. The morphology and size of NPs, characterized by DLS, FE-SEM, TEM, and confocal microscopy, showed smooth and spherical particles with diameters less than 200 nm; Conclusions: In addition, the drug loading, encapsulation efficiency, and drug release profiles, using UV-Vis spectroscopy, showed the highest encapsulation efficiency with 2.5% carboplatin and sustained release profile. [ABSTRACT FROM AUTHOR]

AbstractThe extract of Randia monantha contains high-value biological compounds (HVBC), such as polyphenols with antifungal properties. However, their bio-functional properties are vulnerable to environmental conditions. Ultrasound-assisted emulsification (UAEm) offers a viable protective delivery system. Then, to optimize UAEm conditions for a stable double emulsion supplemented with hydro-ethanolic extract of Randia monantha, a Box-Behnken design was used. The variables included protein fraction (1.3-2%), pre-emulsion ratio (O:W, 1:3.5-1:4.5 mL:mL), and amplitude (40–60%). The response variables were PDI, D[3,2] (µm) and D[4,3] (µm). Response surface methodology revealed that 2% protein fraction concentration, 1:4.5 pre-emulsion ratio (O:W, mL:mL), and a 45% amplitude, produced the emulsion with the lowest PDI (1.10 ± 0.04), D[3,2] (0.57 ± 0.01) and D[4,3] (0.67 ± 0.02). The optimal emulsion completely inhibited Colletotrichum gloeosporioides and Penicillium digitatum mycelial growth, attributed to HVBC protection during emulsification. Furthermore, the emulsion demonstrated both photo and thermal stability, as well as resilience under industrial conditions, including storage time at various temperatures, varying pH, and NaCl concentrations. This highlights the potential use of jackfruit leaf protein fraction as a sustainable plant-based alternative to animal emulsifiers, for the generation of a new biomaterial derived from agricultural waste. [ABSTRACT FROM AUTHOR]

Daucus carota L. extract is attracting interest as a natural colorant alternative. However, the presence of anthocyanins (ACNs), which are sensitive to pH changes, limits its application. To tackle this issue, water-in-oil-in-water (W1/O/W2) double emulsions are emerging as innovative solutions. Nevertheless, the problem of reaching robust colorant systems for industrial use still needs to be overcome. One important target is to reach a high coloring power, minimizing its impact on the final product. In this context, the effect of colorant concentration and the volume of the primary emulsion, two routes to increase the colorant power, on color attributes and stability, an important feature to reach a marketable product, was studied. The optimal experimental design was conducted to two optimal solutions, whether through heightened colorant concentration or primary emulsion volume: a 41/59 (W1/O)/W2 ratio with 11 wt.% colorant, and a 48/52 (W1/O)/W2 ratio with 6 wt.% colorant, respectively. A subsequent assessment of color and physical emulsion stability over 30 days pointed out the solution with the lower colorant concentration (6 wt.%) as the one with better performance (L*: 44.11 ± 0.03, a*: 25.79 ± 0.01, D4;3: 9.62 ± 0.1 µm, and CI: 14.55 ± 0.99%), also minimizing the permeability of the colorant to the outer aqueous phase. Overall, these optimized emulsions offer versatile coloring solutions suitable for various industrial applications, such as food matrices and functional cosmetics. [ABSTRACT FROM AUTHOR]

Due to the increasing global incidence of cancer and the undesirable side effects of conventional therapies, developing drug delivery systems based on nanomaterials is crucial. In this research, a novel and pH-responsive nanocomposite composed of gelatin/polyvinyl alcohol/titanium dioxide (G/PVA/TiO2) was fabricated through water-in-oil-in-water (W/O/W) emulsification and applied for the delivery of the quercetin (QC) drug. The G/PVA/TiO2/QC drug delivery system exhibited 45.7% drug loading and 88.25% encapsulation efficiency due to a high interpenetrating biopolymeric network and the porous structure of TiO2. These values are competitive and higher than those reported for other QC drug delivery systems. FT-IR and XRD analyses confirmed the successful synthesis of the nanocomposite and the crystalline nature of its components. FESEM and zeta potential analyses were conducted to examine the morphology and surface charge, respectively. The zeta potential value of 23.6 mV confirmed the good stability of the nanocomposite. Experiments using the dialysis technique revealed higher amount of QC released in a lower pH environment, mimicking a tumor environment, compared to neutral pH, confirming the pH-sensitivity of the G/PVA/TiO2/QC nanocomposite. Additionally, it exhibited significant cytotoxicity against MCF-7 cells compared to free QC, as indicated by MTT test results. The flow cytometry assay confirmed that G/PVA/TiO2/QC led to a higher apoptotic percentage than free QC, while the free drug showed a higher percentage of necroptotic cells. Schematic illustration depicting the behavior of the QC-loaded nanocomposite at different pHs. [ABSTRACT FROM AUTHOR]

Vitamin C or ascorbic acid, is an organic compound that is highly required by human since it acts as antioxidant, help increase metabolism, and improves the immune system. Vitamin C is easily oxidized and damaged during storage due to several external factors such as light, metal, shear, etc. The encapsulation technique is able to improve the stability as well as the activity of Vitamin C in order to protect the bioactive compound from deleterious external factors. Coconut oil which is composed of about 50% lauric acid, has an antiviral property. This research aimed to obtain the stable water-in-oil-in-water (W1/O/W2) double emulsion using coconut oil upon the incorporation of Vitamin C. Hydrogenated (HCNO) and Medium-Chain Triglycerides (MCT) coconut oil was used as the oil phase, and various emulsifiers such as Tween-20 0.5%, Tween-20 1%, and Tween-20 0.5%/PgPr 0.5% were applied to strengthen the outer interfacial layer. The double emulsion stability was monitored macroscopically, and the destabilization kinetics was studied using the zero and first-order kinetic models. It turned out that the HCNO-based double emulsion demonstrated higher stability compared to the MCT-based double emulsion. The lowest destabilization rate constants of 4.5 x 10-3 h-1 and 6.8 x 10-3 h-1 were obtained for HCNO and MCTbased double emulsions both stabilized with Tween-20 0.5%, respectively. The coconut oil-based double emulsion enriched with Vitamin C would be potentially developed for various functional food applications. [ABSTRACT FROM AUTHOR]

Vitamin C or ascorbic acid, is an organic compound that is highly required by human since it acts as antioxidant, help increase metabolism, and improves the immune system. Vitamin C is easily oxidized and damaged during storage due to several external factors such as light, metal, shear, etc. The encapsulation technique is able to improve the stability as well as the activity of Vitamin C in order to protect the bioactive compound from deleterious external factors. Coconut oil which is composed of about 50% lauric acid, has an antiviral property. This research aimed to obtain the stable water-in-oil-in-water (W1/O/W2) double emulsion using coconut oil upon the incorporation of Vitamin C. Hydrogenated (HCNO) and Medium-Chain Triglycerides (MCT) coconut oil was used as the oil phase, and various emulsifiers such as Tween-20 0.5%, Tween-20 1%, and Tween-20 0.5%/ PgPr 0.5% were applied to strengthen the outer interfacial layer. The double emulsion stability was monitored macroscopically, and the destabilization kinetics was studied using the zero and first-order kinetic models. It turned out that the HCNO-based double emulsion demonstrated higher stability compared to the MCT-based double emulsion. The lowest destabilization rate constants of 4.5 x 10-3 h-1 and 6.8 x 10-3 h-1 were obtained for HCNO and MCT-based double emulsions both stabilized with Tween-20 0.5%, respectively. The coconut oil-based double emulsion enriched with Vitamin C would be potentially developed for various functional food applications.

Abstract Background Curcumin is an age old traditional medicine. Although curcumin has several advantages, its water solubility and bioavailability limit its use as a natural therapeutic agent. Polymeric nano curcumin could be an excellent option to overcome these challenges to augment its therapeutic efficacy. This work aimed to synthesize curcumin-loaded PLGA nanoparticles and assess their angiogenic and antioxidant potential in the zebrafish model. Results The double emulsion solvent evaporation process was employed to make curcumin-loaded PLGA nanoparticles. Curcumin showed ~ 28.23 (± 2.49) encapsulation efficacy with an average diameter of PLGA nanoparticles 168.5 (± 2.5) nm and curcumin nanoparticles about 281.6 (± 17.2) nm, respectively. The curcumin nanoparticles showed no developmental toxicity to the zebrafish embryos while reduced toxicity compared to the native curcumin. Further, the curcumin nanoparticles reduced the generation of reactive oxygen species and improved angiogenesis in the model system. All these results confirmed that the nanoparticle has had higher bio-efficacy than that of native curcumin. Conclusion This study shows that PLGA curcumin nanoparticles hold an excellent therapeutic promise for wound healing, tissue regeneration and other biomedical applications where angiogenesis and ROS play critical role.

Background: Curcumin is an age old traditional medicine. Although curcumin has several advantages, its water solubility and bioavailability limit its use as a natural therapeutic agent. Polymeric nano curcumin could be an excellent option to overcome these challenges to augment its therapeutic efficacy. This work aimed to synthesize curcumin-loaded PLGA nanoparticles and assess their angiogenic and antioxidant potential in the zebrafish model. Results: The double emulsion solvent evaporation process was employed to make curcumin-loaded PLGA nanoparticles. Curcumin showed ~ 28.23 (± 2.49) encapsulation efficacy with an average diameter of PLGA nanoparticles 168.5 (± 2.5) nm and curcumin nanoparticles about 281.6 (± 17.2) nm, respectively. The curcumin nanoparticles showed no developmental toxicity to the zebrafish embryos while reduced toxicity compared to the native curcumin. Further, the curcumin nanoparticles reduced the generation of reactive oxygen species and improved angiogenesis in the model system. All these results confirmed that the nanoparticle has had higher bio-efficacy than that of native curcumin. Conclusion: This study shows that PLGA curcumin nanoparticles hold an excellent therapeutic promise for wound healing, tissue regeneration and other biomedical applications where angiogenesis and ROS play critical role. [ABSTRACT FROM AUTHOR]

Copyright of Food & Fermentation Industries is the property of Food & Fermentation Industries and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aims to evaluate homogenization techniques and conditions for producing stable, small droplet‐size water‐in‐oil (W/O) emulsions intended for incorporation into casein hydrolysate–loaded double emulsions. Three commonly used homogenization methods; rotor–stator, ultrasonic, and high‐pressure homogenization were individually optimized utilizing response surface methodology. Instances of over‐processing were observed, particularly with the rotor–stator and ultrasonic homogenizers under specific conditions. Nevertheless, optimal conditions were identified for each technique: 530 s at 17,800 rpm agitation speed for the rotor–stator homogenizer, 139 s at 39% amplitude for the ultrasonic homogenizer, and 520 s at 1475 bar for the high‐pressure homogenizer. Subsequently, the W/O emulsions produced under optimal conditions and their respective W1/O/W2 double emulsions were compared. The rotor–stator and high‐pressure homogenized W/O emulsions exhibited comparable narrow droplet‐size distributions, as indicated by similar Span values. However, high‐pressure homogenization failed to sufficiently minimize droplet size. Ultrasonic homogenization resulted in droplets at the 1‐μm scale but yielded more polydisperse droplet‐size distribution. According to TOPSIS analysis, an emulsion with a viscosity of 93.1 cP (centiPoise), a stability index of 93.8%, a D(90) of 0.67 μm (0th day), and a D(90) of 0.75 μm (30th day) produced using a rotor–stator was selected. Additionally, double emulsions containing primary emulsions prepared with the rotor–stator method demonstrated higher viscosity, narrower droplet‐size distribution, and lower creaming compared to other samples. This investigation sheds light on the influence of homogenization techniques on emulsion properties, providing valuable insights for optimizing double emulsion formulations. [ABSTRACT FROM AUTHOR]

Double emulsion consists of two interfacial layers which can encapsulate both hydrophilic and lipophilic substances within a single carrier. Besides encapsulation, double emulsion has also been used to modify the sensorial properties of food products. However, at the same time, double emulsion is susceptible to destabilization under environmental stresses and long-term storage. In this paper, recent articles on double emulsion were critically highlighted in terms of production, composition, and stabilization. With current existing fundamental knowledge about double emulsion, this paper aims to review the utilization of double emulsion for food application to bring potential benefits, stability, and future application. The stability of double emulsion during production and storage was affected by the production method, composition, and temperature control. In terms of food application, double emulsion has been successfully applied in fat-reducing products, food encapsulation, fortification, preservation, edible food packaging, etc. The recent insights in forming stable storage of double emulsion with food-grade emulsifiers have also been discussed in this review paper. In the future, the efforts in mitigating the destabilization behaviour of double emulsion might be beneficial in boosting the applications of double emulsion in bigger markets. [ABSTRACT FROM AUTHOR]

Different emulsion systems can be used to deliver bioactive compounds: single, multiple, gel, Pickering, and high internal phase emulsions. Each of them offers advantages and challenges in terms of stability, encapsulation efficiency, and bioactive compound availability during digestion. Moreover, the different emulsion types can affect the quality characteristics of the food products in which they are used, as well as the bioactive compound availability in the complex final matrix. This review provides an overview of the most recent works in this field, divided into two main sections. The first section is focused on in vitro digestibility of emulsion-based delivery systems to highlight the factors that can affect the digestion process and bioactive compound accessibility and availability. The second section is dedicated to the applications of delivery systems in food products, underlining the need for a better evaluation of the emulsion effects on food properties and on the fate of bioactive compounds in the complex matrix. Challenges and perspectives for emulsion-based delivery systems are presented, giving suggestions for future research. [ABSTRACT FROM AUTHOR]

Summary: The study explored the combination effect between of green tea extract (GTE) and black rice extract (BRE) and the encapsulation process of the co‐extract. A 2:1 (w/w) ratio of GTE to BRE in citric aqueous solution at pH 6 showed the highest antioxidant activity (IC50 = 0.306 mg mL−1) with the strongest incremental effect (combination index = 0.547). It exhibited potent anti‐inflammatory effects, with sirtuin 1 enzyme‐stimulating activity (28.593 of fluorescent intensity) and NF‐κB protein suppression in RAW 264.7 macrophages (57.76% at 100 μg mL−1). Freeze‐dried double emulsion encapsulated powder (CEP) with the highest encapsulation efficiency (73.38%) and total polyphenol content (218.28 mg GAE g−1) was prepared using a lecithin to O phase ratio of 2:25 (w/w) and a chitosan‐carboxymethyl cellulose to W1/O emulsion phase ratio of 1:1 (w/w). Our findings suggest utilising CEP as a compound in functional food by contributing to improved health and well‐being. [ABSTRACT FROM AUTHOR]

mRNA delivery systems, such as lipid nanoparticle (LNP), have made remarkable strides in improving mRNA expression, whereas immune system activation operates on a threshold. Maintaining a delicate balance between antigen expression and dendritic cell (DC) activation is vital for effective immune recognition. Here, a water-in-oil-in-water (w/o/w) Pickering emulsion stabilized with calcium phosphate nanoparticles (CaP-PME) is developed for mRNA delivery in cancer vaccination. CaP-PME efficiently transports mRNA into the cytoplasm, induces pro-inflammatory responses and activates DCs by disrupting intracellular calcium/potassium ions balance. Unlike LNP, CaP-PME demonstrates a preference for DCs, enhancing their activation and migration to lymph nodes. It elicits interferon-γ-mediated CD8+ T cell responses and promotes NK cell proliferation and activation, leading to evident NK cells infiltration and ameliorated tumor microenvironment. The prepared w/o/w Pickering emulsion demonstrates superior anti-tumor effects in E.G7 and B16-OVA tumor models, offering promising prospects as an enhanced mRNA delivery vehicle for cancer vaccinations. [Display omitted] [ABSTRACT FROM AUTHOR]

The application of probiotics in functional foods has gained significant interest due to their various beneficial effects to human when consumed in adequate amounts. However, the low survivability of probiotics subjected to adverse environmental conditions during processing, storage and gastrointestinal passage limited their commercial applications. Double emulsion microbial encapsulation is a promising approach to provide probiotic living cells with a full protection to resist adverse environmental conditions. Based on numerous cases of double emulsions applied for probiotic encapsulation, this report reviews various factors influencing the encapsulation yield and viability of probiotics, including emulsification methods, emulsifier selection, effect of probiotics, and modification of emulsification technique, also the targeted release mechanisms of these double emulsions triggered by various manners. This information can be useful to optimize the formulation and emulsification technique of double emulsion in order to improve the use efficacy and beneficial effects of probiotics in different commercial products. [ABSTRACT FROM AUTHOR]

Traditional cancer chemotherapy suffers from low efficacy and severe side effects, limiting its use as a first-line treatment. To address this issue, we investigated a novel way to induce lipid peroxidation (LPO), which plays an essential role in ferroptosis and may be useful against cancer cells and tumors. In this study, a pH-responsive synergistic cancer therapy nanoplatform was prepared using CaCO 3 co-loaded with oleanolic acid (OA) and lipoxygenase (LOX), resulting in the formation OLCaP NP. This nanoplatform exhibited good drug release properties in an acidic tumor environment owing to the presence of CaCO 3. As a result of acidic stimulation at tumor sites, the OLCaP NP released OA and LOX. OA, a chemotherapeutic drug with anticancer activity, is already known to promote the apoptosis of cancer cells, and LOX is a natural enzyme that catalyzes the oxidation of polyunsaturated fatty acids, leading to the accumulation of lipid peroxides and promoting the apoptosis of cancer cells. More importantly, OA upregulated the expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), which promoted enzyme-mediated LPO. Based on our combined chemotherapy and nanocatalytic therapy, the OLCaP NP not only had remarkable antitumor ability but also upregulated ACSL4 expression, allowing further amplification of LPO to inhibit tumor growth. These findings demonstrate the potential of this nanoplatform to enhance the therapeutic efficacy against tumors by inducing oxidative stress and disrupting lipid metabolism, highlighting its clinical potential for improved cancer treatment. This study presents a novel nanoplatform that combines oleanolic acid (OA), a chemotherapeutic drug, and lipoxygenase (LOX), which oxidizes polyunsaturated fatty acids to trigger apoptosis, for targeted cancer therapy. Unlike traditional treatments, our nanoplatform exhibits pH-responsive drug release, specifically in acidic tumor environments. This innovation enhances the therapeutic effects of OA and LOX, upregulating acyl-CoA synthetase long-chain family member 4 expression and amplifying lipid peroxidation to promote tumor cell apoptosis. Our findings significantly advance the existing literature by demonstrating a synergistic approach that combines chemotherapy and nanocatalytic therapy. The scientific impact of this work lies in its potential to improve cancer treatment efficacy and specificity, offering a promising strategy for clinical applications and future research in cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Double emulsion (DE) has recently attracted attention due to its ability to encapsulate hydrophilic and hydrophobic substances and controlled release properties. However, food-grade DE is prone to destabilization due to its complex structure, which makes practical application in the industries difficult. This study investigates the stabilization of DE containing ethanolic kenaf leaf extract using different concentrations of Pickering emulsifier mixture (PEM). PEM consists of sodium caseinate, tween-20, and beta-cyclodextrin at the fixed ratio of 57.9:27.6:14.5% (w/w/w). Key parameters such as droplet size, polydispersity index, creaming index, encapsulation efficiency, and droplet morphology were monitored during 5-week storage at 25 °C. All DE samples remained phase-stable and exhibited increasing viscosity throughout the storage. The droplets displayed a spherical shape, and functional group assessment indicated changes in the molecular interactions after ultrasonic emulsification. DE stabilized by 2.5% and 4.0% (w/w) PEM consistently maintained droplet size and distribution, achieving encapsulation efficiency exceeding 98%. Specifically, DE with 4.0% (w/w) PEM exhibited excellent resistance to pH changes. In conclusion, PEM-stabilized DE remained stable for up to 5 weeks at 25 °C, which facilitates the beneficial uses of double emulsion in food, cosmetic, and medical applications. [ABSTRACT FROM AUTHOR]

Copyright of Modares Mechanical Engineering is the property of Tarbiat Modares University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved products. One potential barrier to the clinical translation of these technologies is a lack of understanding with regard to the manufacturing process, hindering batch scale-up. To address this knowledge gap, we sought to first identify critical processing parameters in the manufacturing process of blank (no therapeutic drug) and protein-loaded double-emulsion poly(lactic-co-glycolic) acid MPs through a quality by design approach. We then utilized the design of experiments as a tool to systematically investigate the impact of these parameters on critical quality attributes (e.g., size, surface morphology, release kinetics, inner occlusion size, etc.) of blank and protein-loaded MPs. Our results elucidate that some of the most significant CPPs impacting many CQAs of double-emulsion MPs are those within the primary or single-emulsion process (e.g., inner aqueous phase volume, solvent volume, etc.) and their interactions. Furthermore, our results indicate that microparticle internal structure (e.g., inner occlusion size, interconnectivity, etc.) can heavily influence protein release kinetics from double-emulsion MPs, suggesting it is a crucial CQA to understand. Altogether, this study identifies several important considerations in the manufacturing and characterization of double-emulsion MPs, potentially enhancing their translation. [ABSTRACT FROM AUTHOR]

Yun Liu,1,2 Timo Hamm,3 Thomas Ralf Eichinger,3 Walter Kamm,3 Heike Andrea Wieland,3 Brigitta Loretz,1 Anna KH Hirsch,2,4 Sangeun Lee,1,2 Claus-Michael Lehr1,2 1Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany; 2Department of Pharmacy, Saarland University, Saarbrücken, Germany; 3Department of Research and Development, Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany; 4Department of Drug Design and Optimisation, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, GermanyCorrespondence: Claus-Michael Lehr, Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany, Tel +49 681 98806-1000, Fax +49 681 98806 1009, Email Claus-Michael.Lehr@helmholtz-hips.de Sangeun Lee, Department of Pharmacy, Saarland University, Saarbrücken, Germany, Tel +49 681 302 4764, Fax +49 681 302 2028, Email Sangeun.Lee@uni-saarland.deBackground: Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.Methods: Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.Results: As a result, the optimized PNCs showed 3-fold encapsulation (< 90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.Conclusion: Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods. Keywords: amphiphilic polymer, nanocomplex, double emulsion, pH-responsive, protein delivery, dynamic covalent chemistry

Daucus carota L. extract is attracting interest as a natural colorant alternative. However, the presence of anthocyanins (ACNs), which are sensitive to pH changes, limits its application. To tackle this issue, water-in-oil-in-water (W1/O/W2) double emulsions are emerging as innovative solutions. Nevertheless, the problem of reaching robust colorant systems for industrial use still needs to be overcome. One important target is to reach a high coloring power, minimizing its impact on the final product. In this context, the effect of colorant concentration and the volume of the primary emulsion, two routes to increase the colorant power, on color attributes and stability, an important feature to reach a marketable product, was studied. The optimal experimental design was conducted to two optimal solutions, whether through heightened colorant concentration or primary emulsion volume: a 41/59 (W1/O)/W2 ratio with 11 wt.% colorant, and a 48/52 (W1/O)/W2 ratio with 6 wt.% colorant, respectively. A subsequent assessment of color and physical emulsion stability over 30 days pointed out the solution with the lower colorant concentration (6 wt.%) as the one with better performance (L*: 44.11 ± 0.03, a*: 25.79 ± 0.01, D4;3: 9.62 ± 0.1 µm, and CI: 14.55 ± 0.99%), also minimizing the permeability of the colorant to the outer aqueous phase. Overall, these optimized emulsions offer versatile coloring solutions suitable for various industrial applications, such as food matrices and functional cosmetics.

This paper uses the Volume of Fluid (VOF) method to simulate a double Co-Flow microfluidic device that can produce double emulsions in both Newtonian (water) and non-Newtonian fluids. The simulation is 2D axisymmetric and involves three phases. A model is evaluated in this study to examine how the size and double emulsion's generation rate are impacted by factors such as phase velocity, viscosities, interfacial tension, and the rheological properties of non-Newtonian fluids. The model predicted the process of emulsification successfully in dripping and jetting regimes and predicted the impacts of phase velocity on the dimension and frequency of compound droplets. Increasing the flow rate of the inner phase causes the inner droplets to grow, while the outer droplet dimensions remain mostly unchanged. Vice versa, an increase in outer phase flow rate reduces compound droplet size. However, when the middle phase's flow rate is enhanced, the size of detached droplets in the inner and outer phases undergoes opposite changes, i.e., decreasing and increasing, respectively. The results showed that in non-Newtonian fluids, smaller droplets are formed compared to water, and the diameter of the double emulsions formed decreases with the rise in the viscosity at zero shear rate of the non-Newtonian fluid. • Double emulsion formation is studied in both Newtonian and non-Newtonian ambient fluids. • By adjusting phase flow rates in Newtonian and non-Newtonian fluids, the double emulsion characteristics can be readily tuned. • The results showed that in non-Newtonian fluids, smaller droplets are formed compared to Newtonian fluid. [ABSTRACT FROM AUTHOR]

The aim of this study was to optimise the microencapsulation efficiency of propolis phenolic compounds by double emulsion solvent evaporation technique (W1/O/W2). The solvent/sample ratio and the polymer and surfactant concentration parameters were optimised using response surface methodology (RSM) through Box–Behnken Design (BBD). For each parameter studied, total phenolic content encapsulation efficiency (TPCEE), free radical scavenging activity (DPPH), and ferric reducing antioxidant power (FRAP) were evaluated. The results showed that the optimal parameters were: 31.60 mg mL−1 for sample/solvent ratio, 606.28 mg mL−1 for poly(ε-caprolactone) (PCL) concentrations, and 2.05 g mL−1 for poly(vinyl alcohol) (PVA) concentration. The optimum values obtained were: 84.62% for encapsulation efficiency of phenolic content, 51.89% for DPPH, and 48,733 mg Trolox Equivalent/100 g dry weight for FRAP. The experimental checking of results revealed the validity of elaborated models and their suitability for the prediction of both responses. The developed mathematical models have expressed a high level of significance through RSM optimisation processes for phenolic antioxidants of propolis. [ABSTRACT FROM AUTHOR]

ABSTRACTThis research studies the impacts of microcrystalline cellulose (MCC) concentrations on the physicochemical properties of spray-dried water-in-oil-in-water (W/O/W) vitamin C double emulsion powder Four MCC concentration (1%, 1.5%, 2%, and 2.5%) were used to produce the vitamin C double emulsion powder. The results of the emulsion’s creaming index, flow behaviour index, zeta value, and particle size indicated that these parameters decreased when the MCC concentration increased. Scanning electronic microscopy (SEM) analysis showed that the higher MCC concentration resulted in a smoother surface In general, the MCC concentration increased, the particle size, hygroscopicity, solubility, water content, and water activity of the double emulsion powder decreased. Double emulsion powder containing 2% MCC presented the highest level of antioxidant activity and was mostly stable after storage for 56 days. Before and after drying, transmission electron microscope (TEM) analysis of the morphological characteristics of the liquid emulsion showed that the concentration of 2% MCC in the emulsion could form a W/O/W double emulsion structure. In conclusion, the addition of MCC significantly affect the properties of vitamin C double emulsion.

This study includes an examination of the design, fabrication, and experimentation of a rudimentary droplet generator. The device has potential applications in on-demand double and higher-order emulsions as well as tailored emulsions with numerous cores. The phenomenon of a pendant double droplet creation is observed when an inner phase is transported through a capillary, while a middle phase envelops the external surface of the capillary. This leads to the occurrence of a pinching-off process at the tip of the pulled capillary. Following this, the double droplet is introduced into a container that is filled with the outer phase. The present study examines the force equilibrium throughout the droplet break-up process and aims to forecast the final morphology of the droplets within the container by considering the impact of interfacial tension ratios. The shell thickness in a core–shell formation can be calculated based on the inner and middle phase flow rates as well as the middle droplet formation period. The present platform, which enables the simple production of double and higher emulsions, exhibits promising prospects for the controlled manufacturing of complex emulsions. This technology holds potential for various applications, including the experimental exploration of collision behavior or electro-hydrodynamics in emulsions as well as millimeter-size engineered microparticle fabrication. [ABSTRACT FROM AUTHOR]

Double emulsions (DEs) present promising applications as alternatives to conventional emulsions in the pharmaceutical, cosmetic, and food industries. However, most review articles have focused on the formulation, preparation approaches, physical stability, and release profile of encapsulants based on DEs, particularly water-in-oil-in-water (W1/O/W2), with less attention paid to specific food applications. Therefore, this review offers updated detailed research advances in potential food applications of both W1/O/W2 and oil-in-water-in-oil (O1/W/O2) DEs over the past decade. To this end, various food-relevant applications of DEs in the fortification; preservation (antioxidant and antimicrobial targets); encapsulation of enzymes; delivery and protection of probiotics; color stability; the masking of unpleasant tastes and odors; the development of healthy foods with low levels of fat, sugar, and salt; and design of novel edible packaging are discussed and their functional properties and release characteristics during storage and digestion are highlighted. [ABSTRACT FROM AUTHOR]

Microcapsules possessing a selective permeability are well‐suited vessels for conducting cell studies or chemical reactions that require selective exchanges of reagents over a prolonged time. Most currently reported microcapsules are single‐use delivery carriers since cargo is only released in significant amounts if their shells are damaged or the release relies on passive diffusion. Stable capsules possessing a selective, rapidly interchangeable permeability, which enables their repeated loading and unloading with selected reagents remain to be shown. Here, capsules are introduced that are composed of thin, viscoelastic, charge‐selective shells made of surfactants that are functionalized with a chelator, 3‐hydroxy‐4‐pyridinonone and crosslinked with appropriate nm‐sized ion clusters, for example composed of Fe3+/Tris or Al3+/Tris ion clusters. The charge selectivity of the shell permeability can be conveniently tuned with the crosslinking ion clusters. It is demonstrated that these capsules can be repeatedly loaded and unloaded with well‐defined substances. This feature enables their application as re‐usable selectively permeable filters to remove certain pollutants from solutions. These capsules are envisaged to be well‐suited for waste water treatment and as picoliter‐sized reaction vessels to selectively conduct chemical reactions within capsule cores while continuously supplying new reagents. [ABSTRACT FROM AUTHOR]

Implementing the Quality by Design (QbD) approach enables pharmaceutical researchers to effectively reduce the number of experimental tests conducted and the associated time required. This aids in identifying important factors that substantially influence the quality of the goods, including vital material characteristics, formulation factors, and crucial procedure factors. This study aims to integrate the advantageous characteristics of Lipid Nanoparticles (LNPs) and the QbD approach to create an innovative Drug Delivery System (DDS) for treating skin cancers and actinic keratosis. LNPs, known for their high efficacy in the topical treatment of skin diseases, were formulated to address the skin layer's intricate structure and facilitate enhanced absorption. The present investigation employed the QbD methodology to fabricate LNP formulations to enhance the dermal permeation of 5-Fluorouracil (5-FU), a commonly utilized agent for treating non-melanoma skin cancer. The Lipid Nanoparticles containing 5-Fluorouracil (5-FLLNP) were synthesized using the Double Emulsion - Solvent Evaporation (DE-SE) technique. The DE-SE involves a dual-stage procedure encompassing two distinct emulsification steps, thereby introducing a heightened level of complexity to the overall process. The stability of nanoparticles produced through a DE-SE method is uncertain due to the various formulations and process attributes involved. Using a DE-SE technique in producing 5- FLLNP is a viable method for DDS, offering a means to achieve a highquality product through implementing the QbD approach. Artificial Neural Networks (ANN) have successfully developed an optimal LNP formulation that ensures quality and falls within the designated Design Space (DS). 5- FLLNP formulation exhibited a greater cell viability of 73% compared to the pure 5-FU formulation, which had a cell viability of 68% for A431 cells. [ABSTRACT FROM AUTHOR]

The encapsulation and release of bioactive compounds obtained from by-products are aspects of exponential boom for several decades, as it seeks to maintain or enhance their activity. A double emulsion (W1/O/W2) was developed with mango seed extract (MS) 'Ataulfo', said extract contains gallic acid and pentagalloyl glucose as major compounds (80.16%). The double emulsion was subjected to release kinetics for 3 h in phosphate buffer (pH 6.9), presenting a release constant (k) of 35,350 ± 6,031 μg/mL/min, in addition to antioxidant capacity by the DPPH and FRAP method of 168,663 ± 4,273 and 39,718 ± 1,019 mMol/g of double emulsion respectively at 120 min of kinetics, the time of 120 min was determined as the latency time (l). The release behavior corresponds to zero-order kinetics since the release of the extract remains constant until the minimum concentration is reached to exert the antioxidant capacity mentioned above. The mechanism of release of the SM extract contained in the double emulsion is governed by diffusion (Fickian behavior), this was determined thanks to the equations of the Korsmeyer-Peppas mathematical model, obtaining a regression adjustment (R2) of 0.9252 for said model and R2 of 0.8126 for zero-order kinetics. The double emulsion was added to a mango peel drink formulation, to which the antitopoisomerase activity was determined in strains of S. cerevisiae (JN394 and JN362a), however, no inhibitory activity was presented towards any strain. The cyclooxygenase inhibition (COX) assay was performed on the 120-minute released fraction and the MS extract, showing that this fraction only showed 18.97% inhibition in COX-II, however, the SM extract obtained an inhibition percentage of 38.14% in COX-II.