Organic nano carbon source inducing 3D silica nanoparticles-graphene nanosheet layer on Cu current collector for high-performance anode-free lithium metal batteries.

Anode-free lithium metal batteries (AFLBs) have attracted considerable attention due to their high theoretical specific capacity and absence of Li. However, the heterogeneous Li deposition and stripping on the lithiophobic Cu collector hamper AFLBs in practice. To achieve a uniform and reversible Li deposition, a carbon-based layer on the Cu collector has attracted intense interest due to its high conductivity. However, the 2D single-component carbon-based interface is inadequate lithiophilic for obtaining the homogeneous Li deposition and preventing the lithium dendrite from piercing the separator. Herein, we present a 3D embedded lithiophilic SiO2 nanoparticles-graphene nanosheet matrix (SiO2@G-M) on the Cu collector by organic nano carbon source. In this structure, the lithiophilic SiO2 nanoparticles as active points promote the homogeneous lithium nucleation and the 3D graphene nanosheet matrix offers homogenous electron distribution and voids to prevent the piercing. Finally, SiO2@G-M/Li cell shows a high coulombic efficiency of 98.62 % after 100 cycles at a high current density of 2 mA cm-2 with an areal capacity of 1 mAh cm-2.

Revelation of adhesive proteins affecting cellular contractility through reference-free traction force microscopy.

Over the past few decades, the critical role played by cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-L-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterial design. In this study, reference-free traction force microscopy with a well-organized microdot array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although poly-L-lysine supported cell spreading and elongation, it was inefficient at inducing cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.

Copious Dislocations Defect in Amorphous/Crystalline/Amorphous Sandwiched Structure P-NiMoO4 Electrocatalyst toward Enhanced Hydrogen Evolution Reaction.

The design and synthesis of efficient, inexpensive, and long-term stable heterostructured electrocatalysts with high-density dislocations for hydrogen evolution reaction in alkaline media and seawater are still a great challenge. An amorphous/crystalline/amorphous sandwiched structure with abundant dislocations were synthesized through thermal phosphidation strategies. The dislocations play an important role in the hydrogen evolution reactions. Copious dislocation defects, combined with cracks, and the synergistic interfacial effect between crystalline phase and amorphous phase regulate the electronic structure of electrocatalyst, provide more active sites, and thus endow the electrocatalysts with excellent catalytic activity under alkaline water and seawater. The overpotentials of P-NiMoO4 at 10 mA/cm2 in 1 M KOH aqueous solution and seawater are 45 and 75 mV, respectively. Additionally, the P-NiMoO4 electrocatalyst exhibits long-term stability over 100 h. This study provides a simple approach for synthesizing amorphous/crystalline/amorphous sandwiched non-noble-metal electrocatalysts with abundant dislocations for hydrogen evolution reaction.

Porous N-Doped Carbon Decorated with Atomically Dispersed Independent Dual Metal Sites from Energetic Zeolite Imidazolate Frameworks as Bidirectional Catalysts for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have ultrahigh theoretical specific capacity and energy density, which are considered to be very promising energy storage devices. However, the slow redox kinetics of polysulfides are the main reason for the rapid capacity decay of Li-S batteries. A reasonable electrocatalyst for the Li-S battery should reduce the reaction barrier and accelerate the reaction kinetics of the bidirectional catalytic conversion of lithium polysulfides (LiPSs), thereby reducing the cumulative concentration of LiPSs in the electrolyte. In this report, porous N-doped carbon nanofibers decorated with independent dual metal sites as catalysts for Li-S batteries were fabricated in one step using a fusion-foaming method. Experimental and theoretical analyses demonstrate that the synergistic effect of independent dual metal sites provides strong LiPS affinity, improved electronic conductivity, and enhanced redox kinetics of polysulfides. Therefore, the assembled Li-S battery exhibits high rate performance (discharge specific capacity of 771 mA h g-1 at 2C) and excellent cycle stability (capacity decay rate of 0.51% after 1000 cycles at 1C).

Three-dimensional carbon network-supported black phosphorus-cobalt heterojunctions: An efficient electrocatalyst for high-rate oxygen evolution.

Black phosphorus (BP), as a burgeoning two-dimensional material, has shown good electrocatalytic activity due to its unique electronic structure and abundant active sites.However, the presence of lone pair electrons in black phosphorus leads to its poor stability and rapid degradation in an oxygen/water environment, which greatly limits its practical application. Herein, BP-Co heterojunctions were synthesized on carbon nanotube@nitrogen-doped carbon (BP-Co/CNT@NC) by the pyrolysis of ZnCo-zeolitic imidazolate frameworks and subsequent solvothermal treatment. The BP-Co Schottky junction improved the electrocatalytic stability of BP, modulated its electronic structure, improved its conductivity and electron transfer during the electrocatalytic reaction. Density functional theory calculation was used to confirm the electron transfer and redistribution at the interface between BP and Co, which constructed an oppositely charged region and formed a strong built-in field. Energy band configuration analysis revealed a narrowed band gap because of the formation of BP-Co Schottky junction. Consequently, the optimized BP-Co/CNT@NC exhibited a superior oxygen evolution reaction (OER) performance, a low overpotential of 370 mV@100 mA/cm2, with a small Tafel slope of 40 mV/dec and good long-term stability. Particularly, the catalyst has an excellent OER performance at the high current density of 100-400 mA/cm2. This strategy improves the stability of BP electrocatalysts and strengthens their utilization in electrocatalytic applications.

Sulfur-deficient MoS2-carbon hollow nanospheres for synergistic trapping and electrocatalytic conversion of polysulfides.

Lithium-sulfur battery is one of the most promising candidates for next-generation energy storage systems, but the serious shuttle effect and sluggish reaction kinetics of polysulfides impair its practical applications. Herein, sulfur-deficient MoS2/carbon hollow nanospheres (MoS2-CHNs) are firstly synthesized by a NaCl-template pyrolysis and employed as sulfur host for lithium-sulfur batteries. TEM analysis reveals that carbon hollow nanospheres existing in the composite are the backbones that help to immobilize the ultrathin MoS2 nanosheets and ensure their large specific surface area. The MoS2 nanosheets consist of 5-10 layers of MoS2 with rich sulfur vacancies. The first principle calculation demonstrates that sulfur vacancy led to an intensively enhanced binding energy (-4.70 eV) towards Li2S6 compared to the pristine MoS2 (-1.57 eV). It suppressed the shuttle effect efficiently. The catalytic experiments reveal that MoS2-CHNs have a superior ability for the nucleation of Li2S and bidirectional electrocatalytic capability for the conversion of polysulfide. The large storage space inside MoS2-CHNs can work as a reservoir for intermediate polysulfides to substantially reduce the concentration overpotential. Due to this advantageous structural design of MoS2-CHNs electrode, its reversible capacity remains 1139 mAh g-1 after 100 cycles at 0.2C, and 600 mAh g-1 after 500 cycles at 5C with a sulfur loading of 5 mg cm-2. Even though the sulfur loading increases to 10 mg cm-2, the Li-S battery delivers a stable capacity of 978 mAh g-1 after 50 cycles at 0.2C. So the MoS2-CHNs demonstrate a promising application for high-energy Li-S batteries.

Promotion of Melanoma Cell Proliferation by Cyclic Straining through Regulatory Morphogenesis.

The genotype and phenotype of acral melanoma are obviously different from UV-radiation-induced melanoma. Based on the clinical data, mechanical stimulation is believed to be a potential cause of acral melanoma. In this case, it is desirable to clarify the role of mechanical stimulation in the progression of acral melanoma. However, the pathological process of cyclic straining that stimulates acral melanoma is still unclear. In this study, the influence of cyclic straining on melanoma cell proliferation was analyzed by using a specifically designed cell culture system. In the results, cyclic straining could promote melanoma cell proliferation but was inefficient after the disruption of cytoskeleton organization. Therefore, the mechanotransduction mechanism of promoted proliferation was explored. Both myosin and actin polymerization were demonstrated to be related to cyclic straining and further influenced the morphogenesis of melanoma cells. Additionally, the activation of mechanosensing transcription factor YAP was related to regulatory morphogenesis. Furthermore, expression levels of melanoma-involved genes were regulated by cyclic straining and, finally, accelerated DNA synthesis. The results of this study will provide supplementary information for the understanding of acral melanoma.

Chemical Energy-Driven Lithiation Preparation of Defect-Rich Transition Metal Nanostructures for Electrocatalytic Hydrogen Evolution.

Transition metal nanostructures are widely regarded as important catalysts to replace the precious metal Pt for hydrogen evolution reaction (HER) in water splitting. However, it is difficult to obtain uniform-sized and ultrafine metal nanograins through general high-temperature reduction and sintering processes. Herein, a novel method of chemical energy-driven lithiation is introduced to synthesize transition metal nanostructures. By taking advantage of the slow crystallization kinetics at room temperature, more surface and boundary defects can be generated and remained, which reduce the atomic coordination number and tune the electronic structure and adsorption free energy of the metals. The obtained Ni nanostructures therein exhibit excellent HER performance. In addition, the bimetal of Co and Ni shows better electrocatalytic kinetics than individual Ni and Co nanostructures, reaching 100 mA cm-2 at a low overpotential of 127 mV. The high HER performance originates from well-formed synergistic effect between Ni and Co by tuning the electronic structures. Density functional theory simulations confirm that the bimetallic NiCo possesses a low Gibbs free energy of hydrogen adsorption, which are conducive to enhance its intrinsic activity. This work provides a general strategy that enables simultaneous defect engineering and electronic modulation of transition metal catalysts to achieve an enhancement in HER performance.

Mo/P Dual-Doped Co/Oxygen-Deficient Co3O4 Core-Shell Nanorods Supported on Ni Foam for Electrochemical Overall Water Splitting.

The exploration for low-cost bifunctional materials for highly efficient overall water splitting has drawn profound research attention. Here, we present a facile preparation of Mo-P dual-doped Co/oxygen-deficient Co3O4 core-shell nanorods as a highly efficient electrocatalyst. In this strategy, oxygen vacancies are first generated in Co3O4 nanorods by lithium reduction at room temperature, which endows the materials with bifunctional characteristics of the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). A Co layer doped with Mo and P is further deposited on the surface of the Co3O4-x nanorods to enhance the electrocatalytic hydrolysis performance. As a result, the overpotentials of HER and OER are only 281 and 418 mV at a high current density of 100 mA cm-2 in 1.0 M KOH, respectively. An overall water electrolytic cell using CoMoP@Co3O4-x nanorods as both electrodes can reach 10 mA cm-2 at 1.614 V with outstanding durability. The improvement is realized by the synergistic effect of oxygen vacancies, Mo/P doping, and core-shell heterostructures for modulating the electronic structure and producing more active sites, which suggests a promising method for developing cost-effective and stable electrocatalysts.

Multifunctional Protection Layers via a Self-Driven Chemical Reaction To Stabilize Lithium Metal Anodes.

The Li metal anode is considered one of the most potential anodes due to its highest theoretical specific capacity and the lowest redox potential. However, the scalable preparation of safe Li anodes remains a challenge. In the present study, a LiF-rich protection layer has been developed using self-driven chemical reactions between the Li3xLa2/3-xTiO3/polyvinylidene fluoride/dimethylacetamide (LLTO/PVDF/DMAc) solution and the Li metal. After coating the LLTO/PVDF/DMAc solution to Li foil, PVDF reacted with Li spontaneously to form LiF, and the accompanying Ti4+ ions (in LLTO) were reduced to Ti3+ to form a mixed ionic and electronic conductor LixLLTO. The protective layer can redistribute the Li-ion transport, regulate the even Li deposition, and inhibit the Li dendrite growth. When paired with LiFePO4, NCM811, and S cathodes, the batteries have demonstrated excellent capacity retention and cycling stability. More importantly, a volumetric energy density of 478 Wh L-1 and 78% capacity retention after 310 cycles have been achieved by using a S/LixLLTO-Li pouch cell. This work provides a feasible avenue to provide large-scale preparation of safe Li anodes for the next-generation pouch-type Li-S batteries as ideal power sources for flexible electronic devices.

Organic molecule confinement reaction for preparation of the Sn nanoparticles@graphene anode materials in Lithium-ion battery.

Sn@Graphene composites as anode materials in Lithium-ion batteries have attracted intensive interest due to the inherent high capacity. On the other side, the high atomic ratio (Li4.4Sn) induces the pulverization of the electrode with cycling. Thus, suppressing pulverization by designing the structure of the materials is an essential key for improving cyclability. Applying the nanotechnologies such as electrospinning, soft/hard nano template strategy, surface modification, multi-step chemical vapor deposition (CVD), and so on has demonstrated the huge advantage on this aspect. These strategies are generally used for homogeneous dispersing Sn nanomaterials in graphene matrix or constructing the voids in the inner of the materials to obtain the mechanical buffer effect. Unfortunately, these processes induce huge energy consumption and complicated operation. To solve the issue, new nanotechnology for the composites by the bottom-up strategy (Organic Molecule Confinement Reaction (OMCR)) was shown in this report. A 3D organic nanoframes was synthesized as a graphene precursor by low energy nano emulsification and photopolymerization. SnO2 nanoparticles@3D organic nanoframes as the composites precursor were in-situ formed in the hydrothermal reaction. After the redox process by the calcination, the Sn nanoparticles with nanovoids (~100 nm, uniform size) were homogeneously dispersed in a Two-Dimensional Laminar Matrix of graphene nanosheets (2DLMG) by the in-situ patterning and confinement effect from the 3D organic nanoframes. The pulverization and crack of the composites were effectively suppressed, which was proved by the electrochemical testing. The Sn nanoparticles@2DLMG not delivered just the high cyclability during 200 cycles, but also firstly achieved a high specific capacity (539 mAh g-1) at the low loading Sn (19.58 wt%).

Multidrug-loaded electrospun micro/nanofibrous membranes: Fabrication strategies, release behaviors and applications in regenerative medicine.

Electrospun micro/nanofibrous membranes (EFMs) have been widely investigated as local drug delivery systems. Multiple drugs can be simultaneously incorporated into one EFM to create synergistic effects, reduce side effects, and play their respective roles in the complex physiological processes of tissue regeneration and postoperative adhesion prevention. Due to the versatile electrospinning techniques, sustained and programmed release behaviors of multiple drugs could be achieved by modulating the structure of the EFMs and the location of the drugs. In this review, various multidrug incorporation approaches based on electrospinning are overviewed. In particular, the advantages and limitations of each drug incorporation technique, the methods to control drug release and the effect of one drug release on another are discussed. Then the applications of multidrug-loaded EFMs in regenerative medicine, including wound healing, bone regeneration, vascular tissue engineering, nerve regeneration, periodontal regeneration and adhesion prevention are comprehensively reviewed. Finally, the future perspectives and challenges in the research of multidrug-loaded EFMs are discussed.

Tuning the Band Structure of MoS2 via Co9S8@MoS2 Core-Shell Structure to Boost Catalytic Activity for Lithium-Sulfur Batteries.

The introduction of a dual-functional interlayer into lithium-sulfur batteries (LSBs) provides many opportunities for restraining the "shuttle effect" and enhancing sluggish sulfur conversion kinetics. Tuning the band structure of the metal sulfide provides an opportunity to enhance its catalytic activity, which plays an important role in suppressing the "shuttle effect" of lithium polysulfides (LiPSs) in LSBs. Here were present a Co9S8@MoS2 core-shell heterostructure anchored to a carbon nanofiber (Co9S8@MoS2/CNF), developed as an interlayer for suppressing the shuttle effect of LiPSs. The fabricated composite heterostructure is determined to be an effective alternative material that combines the synergistic relationship between chemisorption and electrochemical catalysis. We find that the band structure of the MoS2 shell can be effectively tuned by the Co9S8 core and that the Co9S8@MoS2/CNF can capture the LiPSs, providing excellent catalytic ability to convert LiPSs into Li2S2, with subsequent transformation from Li2S2 to Li2S. Importantly, high capacities of 1002 and 986 mAh g-1 can be retained after 50 cycles with high-sulfur loadings of 6 and 10 mg cm-2. Our results highlight the design of an atomic-scale heterostructure as a multifunctional interlayer providing a synergistic relationship between adsorption and catalysis. The net result is an effective retardation of the shuttling of LiPSs and an enhancement of the electrochemical redox reactions of LiPSs. This work shows great promise toward the development of practical applications of LSBs.

Production of lipophilic nanogels by spontaneous emulsification.

Nanosized gel particles, so-called nanogels, have attracted substantial interest in different application fields, thanks to their controllable and three-dimensional physical structure, good mechanical properties and potential biocompatibility. Literature reports many technologies for their preparation and design, however a recurrent limitation remains in their broad size distributions as well as in the poor size control. Therefore, the monodisperse and size-controlled nanogels preparation by simple process -like emulsification- is a real challenge still in abeyance to date. In this study we propose an original low energy emulsification approach for the production of monodisperse nanogels, for which the size can be finely controlled in the range 30 to 200 nm. The principle lies in the fabrication of a direct nano-emulsion containing both oil (medium chain triglycerides) and a bi-functional acrylate monomer. The nanogels are thus formed in situ upon UV irradiation of the droplet suspension. Advantage of such modification of the oil nano-carriers are the potential modulation of the release of encapsulated drugs, as a function of the density and/or properties of the polymer chain network entrapped in the oil nano-droplets. This hypothesis was confirmed using a model of hydrophobic drug -ketoprofen- entrapped into the nanogels particles, along with the study of the release profile, carried out in function of the nature of the monomers, density of polymer chains, and different formulation parameters.

Preparation and Deep Characterization of Composite/Hybrid Multi-Scale and Multi-Domain Polymeric Microparticles.

Polymeric microparticles were produced following a three-step procedure involving (i) the production of an aqueous nanoemulsion of tri and monofunctional acrylate-based monomers droplets by an elongational-flow microemulsifier, (ii) the production of a nanosuspension upon the continuous-flow UV-initiated miniemulsion polymerization of the above nanoemulsion and (iii) the production of core-shell polymeric microparticles by means of a microfluidic capillaries-based double droplets generator; the core phase was composed of the above nanosuspension admixed with a water-soluble monomer and gold salt, the shell phase comprised a trifunctional monomer, diethylene glycol and a silver salt; both phases were photopolymerized on-the-fly upon droplet formation. Resulting microparticles were extensively analyzed by energy dispersive X-rays spectrometry and scanning electron microscopy to reveal the core-shell morphology, the presence of silver nanoparticles in the shell, organic nanoparticles in the core but failed to reveal the presence of the gold nanoparticles in the core presumably due to their too small size (c.a. 2.5 nm). Nevertheless, the reddish appearance of the as such prepared polymer microparticles emphasized that this three-step procedure allowed the easy elaboration of composite/hybrid multi-scale and multi-domain polymeric microparticles.

Li0.35La0.55TiO3 Nanofibers Enhanced Poly(vinylidene fluoride)-Based Composite Polymer Electrolytes for All-Solid-State Batteries.

Using polymer electrolytes with relatively high mechanical strength, enhanced safety, and excellent flexibility to replace the conventional liquid electrolytes is an effective strategy to curb the Li-dendrite growth in Li-metal batteries (LMBs). However, low ionic conductivity, unsatisfactory thermal stability, and narrow electrochemical window still hinder their applications. Here, we fabricate Li0.35La0.55TiO3 (LLTO) nanofiber-enabled poly(vinylidene fluoride) (PVDF)-based composite polymer electrolytes (CPEs) with enhanced mechanical property and wide electrochemical window. The results show that 15 wt % of LLTO nanofibers synergize with PVDF, giving a flexible electrolyte membrane with significantly improved performance, such as high ionic conductivity (5.3 × 10-4 S cm-1), wide electrochemical window (5.1 V), high mechanical strength (stress 9.5 MPa, strain 341%), and good thermal stability (thermal degradation 410 °C). In addition, an all-solid-state Li-metal battery of sandwich-type LiFePO4/PVDF-CPE (15 wt % of LLTO)/Li delivers satisfactory cycling stability and outstanding rate performance. A reversible capacity of 121 mA h g-1 is delivered at 1 C after 100 cycles. This work exemplifies that the introduction of LLTO nanofibers can improve the electrochemical performances of PVDF-based CPEs used as electrolytes for all-solid-state LMBs.

Double emulsions prepared by two-step emulsification: History, state-of-the-art and perspective.

Attractive interest on double emulsions comes from their unique morphology, making them general multifunctional carriers able to encapsulate different hydrophilic and lipophilic molecules in the same particle. Over the past century, two different types of methods were followed to prepare double emulsions for pharmaceutics applications, so-called "one-step" and "two-step" processes. The two-step approach, consisting in two different emulsifications successively performed, allows the optimal and more efficient formulations due to simplicity of principle and controllability of the process. In this review, focused on the formulation of double emulsions by two-step process, we recount the historical development of this approach, along with the state-of-the-art, including a discussion on the role of the formulation parameters, surfactants, amphiphilic polymers, interface stabilization, volume fraction, and so forth, on the final formulation stability, morphology and properties as drug delivery system. Discussion was also extended to polymeric microparticles and nanoparticles made by solvent diffusion, on the basis of double emulsions made by two-step process, along with literature review on the impact of different formulation and processing parameters. In addition, the properties of the polymers used in the microparticles matrix (molecular weight, chemical nature) potentially impacting on the ones of the microparticles formed (drug release kinetics, stability, morphology), were also discussed. Finally, the future trends in double emulsions application were addressed, emphasizing some new advances made in the emulsifications method as potentially able to open the range of applications, for example to nanoscale with spontaneous emulsification or low energy microfluidic emulsification.

Production of dry-state ketoprofen-encapsulated PMMA NPs by coupling micromixer-assisted nanoprecipitation and spray drying.

We present a two-step process to produce dry-state Ketoprofen-loaded poly(methyl methacrylate) nanoparticles (NPs) with controllable size and tunable drug release profile. A colloidal suspension of drug-loaded nanoparticles was first obtained from a nanoprecipitation process and then transferred into a commercial spray dryer. Three micromixers of different designs and mixing principles (molecular diffusion and impact mixing) were tested. After the first step, highly monomodal NPs in the size range 100 to 210 nm were obtained as seen by the low polydispersity index value (ca. PDI ∼ 0.2) returned by a dynamic light scattering detector. Physicochemical properties, encapsulation efficiency/ratio and drug release kinetics of NPs before and after drying were determined. For similar operating conditions, the best micromixer tested (impact mixing) allowed concluding that the NPs size was not significantly affected by the spray drying while encapsulation parameters and drug release rate were slightly decreased compared to the non spray-dried NPs. A sustained drug release was observed over 6 h and the drug release rate (up to 70%) was found to vary with the size of the NPs which in turn was a function of the flow rate ratio between the polymer solution and the non-solvent solution.

Microfluidic-Assisted Production of Size-Controlled Superparamagnetic Iron Oxide Nanoparticles-Loaded Poly(methyl methacrylate) Nanohybrids.

In this paper, superparamagnetic iron oxide nanoparticles (SPIONs, around 6 nm) encapsulated in poly(methyl methacrylate) nanoparticles (PMMA NPs) with controlled sizes ranging from 100 to 200 nm have been successfully produced. The hybrid polymeric NPs were prepared following two different methods: (1) nanoprecipitation and (2) nanoemulsification-evaporation. These two methods were implemented in two different microprocesses based on the use of an impact jet micromixer and an elongational-flow microemulsifier. SPIONs-loaded PMMA NPs synthesized by the two methods presented completely different physicochemical properties. The polymeric NPs prepared with the micromixer-assisted nanoprecipitation method showed a heterogeneous dispersion of SPIONs inside the polymer matrix, an encapsulation efficiency close to 100 wt %, and an irregular shape. In contrast, the polymeric NPs prepared with the microfluidic-assisted nanoemulsification-evaporation method showed a homogeneous dispersion, an almost complete encapsulation, and a spherical shape. The properties of the polymeric NPs have been characterized by dynamic light scattering, thermogravimetric analysis, and transmission electron microscope. In vitro cytotoxicity assays were also performed on the nanohybrids and pure PMMA NPs.

A new method for the formulation of double nanoemulsions.

Double emulsions are very attractive systems for many reasons; the most important of these are their capacity to encapsulate hydrophilic and lipophilic molecules simultaneously in a single particle and their potentiality to protect fragile hydrophilic molecules from the continuous phase. Double emulsions represent a technology that is widely present down to the micrometer scale; however, double nanoemulsions, with their new potential applications as nanomedicines or diagnosis agents, currently present a significant challenge. In this study, we propose an original two-step approach for the fabrication of double nanoemulsions with a final size below 200 nm. The process consists of the formulation of a primary water-in-oil (w1/O) nanoemulsion by high-pressure homogenization, followed by the re-emulsification of this primary emulsion by a low-energy method to preserve the double nanostructure. Various characterization techniques were undertaken to confirm the double structure and to evaluate the encapsulation efficiency of a small hydrophilic probe in the inner aqueous droplets. Complementary fluorescence confocal and cryo-TEM microscopy experiments were conducted to characterize and confirm the double structure of the double nanoemulsion.