Search Results (66)

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery. Full article

The rheology of dilute emulsions is reviewed comprehensively. The fundamental equations governing the flow fields inside and outside the droplets are discussed, along with the boundary conditions. The rheological constitutive law for dilute emulsions with pure interfaces characterized by interfacial tension is developed using the flow field external to the droplets. Both zero-order and first-order deformations of droplets are considered. Dilute emulsions exhibit non-Newtonian behavior. The influences of surface charge and surfactants on the emulsion rheology are covered in detail. The rheology of emulsions of double droplets and droplets covered with elastic membranes is covered as well. Finally, a significant section of the review is focused on the dynamic rheology of dilute emulsions. Emulsions with pure interfaces and additive-laden interfaces are considered. The theories developed for the dynamic rheology of emulsions consisting of different types of interfaces are reviewed, including purely viscous interfaces, purely elastic interfaces, viscoelastic interfaces, and interfaces possessing bending rigidity. In general, the theory for dilute emulsion rheology is well developed. Our current understanding of dilute emulsion rheology is good from a theoretical point of view. A priori predictions of dilute emulsion rheology are possible using the existing theories. However, serious gaps in the existing knowledge on dilute emulsion rheology remain. This review identifies the gaps in existing knowledge and points out future directions in research related to dilute emulsion rheology. Full article

The term “pristine emulsion” is used for differentiating emulsions that consist of only water and oil with no surfactant from the Pickering emulsions, which are also surfactant-free but stabilized with colloidal particles. We review 22 papers dedicated to such emulsions prepared from a wide variety of liquids. We studied here the evolution of one such emulsion, hexadecane-in-water at 4% vl, over a long period of time, from days to weeks. We discovered that the droplet size grows with time, with a rate that depends on mixing conditions, which supports a coalescence hypothesis. However, this coalescence is unusual because the size reaches a certain constant value, which contradicts typical coalescence behavior. To explain this peculiarity and such emulsification in general, we employ a theoretical model that was developed for explaining pristine nano-bubble stability. We hypothesize the existence of a layer of structured water molecules at the interface, following Eastoe and Ellis (Adv in Colloid and Interface Sci., 134–135, 89–95, 2007) and others. We point out that the Electric Double Layer exerts a force on the water dipole moments in this layer (dielectrostatic force) that compensates Kelvin’s pressure. The droplet size calculated using this model is close to the measured size. The second factor associated with this layer is the repulsion of the water dipole moments, which we show can compensate for the surface tension tangential to the interface. After ruling out alternative hypotheses with our data, we conclude that the model suggested for explaining the stability of nano-bubbles is also consistent with our results for these “pristine emulsions”. Full article

Thyme oil (TO) is emerging as a promising candidate to counteract antimicrobial resistance due to its renowned antimicrobial and anti-inflammatory properties. However, rapid gastric absorption of its bioactive compounds limits its intestinal delivery, where its action is required, so the protection of these components is necessary. This pilot study optimized TO-loaded emulsions for targeted intestinal release. High-shear homogenization and membrane emulsification were compared to formulate single oil in water (O/W) and double water in oil in water (W/O/W) emulsions, screening emulsifiers (lecithin, Tween 20, Tween 80) and functional biopolymers (pectin, sodium alginate). High-shear homogenization with lecithin (0.5%), pectin (1.80%), and sodium alginate (0.2%) yielded stable submicron O/W emulsion (Span = 0.5; d(v,0.5) = 0.21 µm), achieving electrostatic stabilization (ζ-potential = −51.5 ± 1.5 mV) at a target poultry dosage. A pH-responsive behavior was observed: protective hydrogel formed in gastric conditions (d(v,0.5) = 2.64 µm) and maintained stability at intestinal pH (d(v,0.5) = 3.03 µm). Membrane emulsification enabled precise droplet control under mild conditions, producing monodisperse O/W emulsions (d(v,0.5) = 38–59 µm; Span ≤ 1.0) and W/O/W double emulsions (d(v,0.5) = 26.5 µm; Span = 0.6) with ultra-low interfacial tension (0.52 mN·m⁻¹). Repeated membrane passes reduced droplet size to ~6.6 µm. These systems represent a foundational step toward bioactive intestinal delivery, providing a viable antibiotic-free strategy for sustainable livestock production. Full article

This study investigates the formulation and optimization of acid-stable water-in-oil-in-water (W/O/W) double emulsions stabilized by sodium caseinate (NaCN)–xanthan gum (XG) complexes, with the aim of developing a natural biopolymer-based delivery system exhibiting controlled release behavior. The emulsions were prepared at pH 4, and the effects of NaCN concentration, XG concentration, and primary fraction (PF) on the encapsulation efficiency (EE) and droplet size (DS) were systematically evaluated using response surface methodology (RSM) based on a Box–Behnken design (BBD). Microscopic and rheological analyses confirmed the formation of a rigid interfacial film around the droplets, leading to improved emulsion stability over one month of storage at 4, 25, and 40 °C. The release kinetics of chlortetracycline (CTC), used as a model drug, followed a Fickian diffusion mechanism, indicating efficient control of the release rate by the NaCN/XG interfacial complex. The optimized formulation (NaCN = 0.652%, XG = 0.339%, PF = 10%) yielded an encapsulation efficiency of 87.7% and a mean droplet size of 24.83 µm, demonstrating excellent predictive accuracy of the statistical model. The results highlight the potential of NaCN/XG complexes to produce acid-stable, biopolymer-based double emulsions capable of sustained release of bioactive compounds, making this system promising for food and pharmaceutical delivery applications. Full article

Microfluidic device prototyping demands rapid, cost-effective, and high-precision mould fabrication, yet ultrashort pulsed laser structuring of polymer inserts remains underexplored. This study presents a novel method for fabricating microfluidic mould inserts using femtosecond (fs) laser ablation of polyimide (PI) films, achieving high precision from design to prototype. PI films (250 µm) were structured using a 355 nm fs laser (300 fs, 500 kHz, 0.95 J/cm²) in a photochemically dominated ablation regime and bonded to reusable steel plates. Injection moulding trials with cyclic olefin copolymer (COC) and polymethyl methacrylate (PMMA) were conducted with diverse designs, including concentration gradient generators (CGG), organ-on-chip (OOC) with 20 µm bridges, and double emulsion droplet generators (DEDG) with 100–500 µm channels, ensuring robustness across complex geometries. The method achieved near 1:1 replication (errors < 2%, microchannel height tolerances < 1%, Sa = 0.02 µm in channels, 0.26 µm in laser-structured areas), machining times under 2 h, and mould durability over 100 cycles without significant deterioration. The PI’s heat-retarding effect mimicked variothermal moulding, ensuring complete micro-penetration without specialised equipment. By reducing material costs using PI films and reusable steel plates, enabling rapid iterations within hours, and supporting industry-compatible prototyping, this approach lowers barriers for small-scale labs. It enables rapid prototyping of diagnostic lab-on-chip devices and supports decentralised manufacturing for biomedical, chemical, and environmental applications, offering a versatile, cost-effective tool for early-stage development. Full article

The production of water-in-water emulsion droplets, the coalescence of which is prevented by adding oil-in-water micrometric droplets, is reported. Hexadecane (O) and cetyl trimethyl ammonium bromide (CTAB) were added to a W/W emulsion made of dextran (Dex)-enriched droplets in a Polyethyleglycol (PEG)-enriched continuous phase, and the mixture was further sonicated. Using Nile red to label the oil droplets enabled the observation of their presence at the surface of Dex droplets (5 µm), allowing for stabilizing them, preventing coalescence of the W/W emulsion, and mimicking W/O/W double emulsions. The addition of sulfate derivative of Dextran (DexSulf) allowed for stable droplets of a slightly larger diameter. By contrast, the addition of carboxymethyl Dextran (CMDex) destabilized the initial aqueous double-like emulsion, yielding sequestration of the oil droplets within the Dex-rich phase. Interestingly, addition of DexSulf to that unstable emulsion re-yielded stable droplets. Similar findings (destabilization) were obtained when adding sodium dodecyl sulfate (SDS) to the initial double-like emulsion, which reformed stable droplets when adding positively charged Dextran (DEAEDex) derivatives. The use of fluorescently (FITC) labeled derivatives of Dextran (Dex, CMDex, DEAEDex, and DexSulf) allowed us to follow their position within, out of, or at the interface of droplets in the above-mentioned mixtures. These findings are expected to be of interest in the field of materials chemistry. Full article

Optically triggering the core coalescence of double-emulsion droplets remains challenging. Herein, we utilize a photovoltaic field generated by laser illumination on LiNbO₃ crystals to trigger the core coalescence in a high-throughput manner. The synergy between the interfacial pressure of the shell droplet and the internal flow induced by the photovoltaic field facilitates the core coalescence. With an increase in the core number, the illumination intensity required for the core coalescence is found to increase initially, whereas it tends to saturate at 5 × 10⁷ W/m², an intensity that does not cause a large temperature increase (<4 °C). The effective mixing of the substances contained in two core droplets after their coalescence is also verified. The proposed technique provides a precise, non-thermal and electrodeless strategy for high-throughput biochemical microreactions. Full article

Thus far, the focus of research has been on employing perilla seed protein isolate (PSPI) to stabilize emulsions encapsulating hydrophobic substances, but there is a dearth of studies focusing on PSPI-stabilized double emulsions for encapsulating hydrophilic materials. This experiment investigated the environmental stability (thermal, ionic strength, and freeze–thaw stability) of PSPI-stabilized double emulsions encapsulating anthocyanins. During thermal stability experiments, the emulsion color lightened as the treatment temperature increased, whereas the microstructures of the emulsions exhibited no notable differences among the groups. The anthocyanin retention and antioxidant capacity decreased with increasing thermal treatment temperature. After thermal treatment, no creaming or separation was observed, and anthocyanin retention remained above 65% in all groups. Ionic strength exerted a certain influence on the stability of the emulsions, with droplet size increasing and anthocyanin retention dwindling as ionic strength intensified. At an ionic strength of 100 mmol/L, anthocyanin retention surpassed 70%. No delamination was observed at any of the ionic strengths. With the augmentation of freeze–thaw cycles, the emulsions darkened and yet remained unseparated, droplet size progressively increased, and anthocyanin retention progressively decreased. The findings indicate that the emulsions were environmentally stable and could serve as a reference for the development of related emulsions. Full article

Background/Objectives: Double emulsions (DEs) enable the simultaneous encapsulation of water-soluble and oil-soluble bioactive compounds. Their stability can be enhanced through Pickering stabilization, where solid particles are irreversibly anchored at the interfaces, forming a steric barrier. This study aimed to evaluate the release behavior of curcumin and chlorogenic acid (CA) in Pickering DEs formulated with chitin nanocrystals (ChNCs) stabilizing the outer interface (DE-ChNC) and both ChNCs and myristic acid-functionalized silica nanoparticles (SNPs-C14) stabilizing the outer and inner interfaces (DE-ChNC-C14) under in vitro gastrointestinal digestion. Methods: The optimal homogenization parameters (time and speed) for stabilizing the external interface with ChNCs were determined using a statistical design. Pickering DEs were characterized (droplet size and size distribution, microstructure, creaming, encapsulation efficiency and stability, rheological behavior) and subjected to the INFOGEST digestion method. Results: ChNCs effectively maintained the droplet size, microstructure, and ζ-potential, preventing coalescence and creaming while enhancing viscosity and gel-like behavior, contributing to improved physical stability. The CA encapsulation efficiency was higher in DE-ChNC-C14 (91.4%) than in DE-ChNC (45.0%) due to the presence of SNPs-C14 at the inner interface, which improved CA retention during storage. CA was gradually released from DE-ChNC-C14 throughout digestion, with bioaccessibility similar to that of the control DE (stabilized with conventional emulsifiers; ~60%). Curcumin bioaccessibility in the Pickering DEs was relatively high (~40%) but lower than in the control DE, as the ChNCs reduced lipid digestion and curcumin bioaccessibility. Conclusions: ChNCs and SNPs-C14 effectively stabilized the outer and inner interfaces of DEs, enabling the simultaneous release of water-soluble and oil-soluble bioactives with health benefits. Full article

The low stability of water-in-oil-in-water (W₁/O/W₂) double emulsions greatly limits their applications. Therefore, in this study, W₁/O/W₂ Pickering double emulsions (PDEs) were prepared by a two-step emulsification method using polyglycerol polyricinoleate (PGPR) and xanthan gum/lysozyme nanoparticles (XG/Ly NPs) as lipophilic and hydrophilic emulsifiers, respectively. The regulation mechanism of the performance of PDEs by XG/Ly NPs was investigated, and the ability of the system to co-encapsulate epigallocatechin gallate (EGCG) and β-carotene was evaluated. The results showed that increasing the XG/Ly NPs concentration can enhance the stability of PDEs. At 60% W₂ phase percentage and 2.0% XG/Ly NPs, the PDEs showed a smaller droplet size (23.47 ± 2.28 μm) and no phase separation after 21 days of storage. Additionally, the PDEs co-encapsulated system showed higher encapsulation efficiency (EGCG: 89.21%; β-carotene: 99.14%) and maintained high retention of active substances after 8 h of UV illumination (EGCG: 75.51%; β-carotene: 77.24%). As demonstrated by in vitro simulated gastrointestinal digestion assays, the bioaccessibility of EGCG and β-carotene simultaneously encapsulated was improved by 66.0% and 36.2%, respectively, compared with that of individually encapsulated EGCG and β-carotene. Overall, this study provides a new reference for the construction of highly stable PDEs and is promising as a co-encapsulation carrier for environmentally sensitive components. Full article

The encapsulation of bacteria in emulsion droplets offers various advantages over other conventional methods of encapsulation, such as improvements in bacterial viability, and may serve as microenvironments for bacterial growth. Nevertheless, changes in temperature may affect bacterial viability and droplet stability. In this study, the encapsulation of bacteria in single water-in-oil (W/O) and double water-in-oil-in-water (W₁/O/W₂) emulsions under cold storage and temperature-modulated release were investigated. The microencapsulation of bacteria in emulsion droplets was achieved by using a flow-focusing microfluidic device. Droplet stability was determined by measuring changes in droplet size and creaming behaviour at different temperatures. The thermal properties of the samples were determined by using differential scanning calorimetry, while the release of bacteria with changes in temperature was determined by measuring the colony form unit (CFU) of the released bacteria and conducting fluorescence microscopy. Higher bacterial viability was observed for encapsulated samples compared to free cells, indicating the ability of the emulsion system to improve bacterial viability during cold-temperature storage. The crystallisation temperature was lowered in the presence of bacteria, but the melting temperature was similar with or without bacteria. Storage in freezing temperatures of −20 °C and −80 °C led to extensive droplet destabilisation, with the immediate release of encapsulated bacteria upon thawing, where the temperature-modulated release of encapsulated bacteria was achieved. This study provides an overview of the potential application of emulsion droplets for bacterial encapsulation under cold-temperature storage and the controlled release of encapsulated bacteria mediated by changes in temperature, which is beneficial for various applications in industries such as food and pharmaceuticals. Full article

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (S_mix) of Cremophore^® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low S_mix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin. Full article

Microfluidics offers a highly controlled and reproducible route to synthesize lipid vesicles. In recent years, several microfluidic approaches have been introduced for this purpose, but double emulsions, such as Water-in-Oil-in-Water (W/O/W) droplets, are preferable to produce giant vesicles that are able to maximize material encapsulation. Flow focusing (FF) is a technique used to generate double emulsion droplets with high monodispersity, a controllable size, and good robustness. Many researchers use polydimethylsiloxane as a substrate material to fabricate microdroplet generators, but it has some limitations due to its hydrophobicity, incompatibility with organic solvents, and the molecular adsorption on the microchannel walls. Thus, specific surface modification and functionalization steps, which are uncomfortable to perform in closed microchannels, are required to overcome these shortcomings. Here, we propose glass as a material to produce a chip with a six-inlet junction geometry. The peculiar geometry and the glass physicochemical properties allow for W/O/W droplet formation without introducing microchannel wall functionalization and using a variety of reagents and organic solvents. The robust glass chip can be easily cleaned and used repeatedly, bringing advantages in terms of cost and reproducibility in emulsion preparation. Full article

The droplet microfluidic device has become a widely used tool in fields such as physics, chemistry, and biology, but its complexity has limited its widespread application. This report introduces a modular and cost-effective droplet microfluidic device for the controlled production of complex emulsions, including oil and aqueous single emulsions, and double emulsions with varying numbers of encapsulated droplets. The droplet sizes can be precisely controlled by easily replacing flat needles and adjusting the needle position within an axially accelerated co-flow field. This modular device not only allows for easy repair and maintenance in case of device clogging or damage but can also be readily expanded to produce complex emulsions. The low-cost and user-friendly nature of the device greatly facilitates the widespread adoption and utilization of droplet microfluidics. Full article