Mechanisms and Control of Self-Emulsification upon Freezing and Melting of Dispersed Alkane Drops

Emulsification requires drop breakage and creation of a large interfacial area between immiscible liquid phases. Usually, high-shear or high-pressure emulsification devices that generate heat and increase the emulsion temperature are used to obtain emulsions with micrometer and submicrometer droplets. Recently, we reported a new, efficient procedure of self-emulsification (Tcholakova et al. Nat. Commun. 2017, 8, 15012), which consists of one to several cycles of freezing and melting of predispersed alkane drops in a coarse oil-in-water emulsion. Within these freeze-thaw cycles of the dispersed drops, the latter burst spontaneously into hundreds and thousands of smaller droplets without using any mechanical agitation. Here, we clarify the main factors and mechanisms, which drive this self-emulsification process, by exploring systematically the effects of the oil and surfactant types, the cooling rate, and the initial drop size. We show that the typical size of the droplets, generated by this method, is controlled by the size of the structural domains formed in the cooling-freezing stage of the procedure. Depending on the leading mechanism, these could be the diameter of the fibers formed upon drop self-shaping or the size of the crystal domains formed at the moment of drop-freezing. Generally, surfactant tails that are 0-2 carbon atoms longer than the oil molecules are most appropriate to observe efficient self-emulsification. The specific requirements for the realization of different mechanisms are clarified and discussed. The relative efficiencies of the three different mechanisms, as a function of the droplet size and cooling procedure, are compared in controlled experiments to provide guidance for understanding and further optimization and scale-up of this self-emulsification process

Bottom-Up Synthesis of Polymeric Micro- and Nanoparticles with Regular Anisotropic Shapes

Shape-anisotropic polymeric micro- and nanoparticles are of significant interest for the development of novel composite materials, lock-and-key assemblies, and drug carriers. Currently, syntheses require external confinement in microfluidic devices or lithographic techniques associated with significant infrastructure and low productivity, so new methods are necessary to scale-up such production efficiently. Here we report bottom-up polymerization of regular shape-anisotropic particles (polygonal platelets with different numbers of edges, with and without protruding asperities, and fibrilar particles with controllable aspect ratios), with size control over 4 orders of magnitude (∼50 nm-1 mm). Polymerization also enables the study of much smaller shapes than could previously be studied in water suspensions, and we study the fundamental limits of the self-shaping transition process driving these transformations for monomer oil droplets of stearyl methacrylate (SMA) monomer oil. We show the method is compatible with a variety of polymerizing monomers and functional modifications of the particles (e.g., composites with magnetic nanoparticles, oil-soluble additives, etc.). We also describe postsynthetic surface modifications that lead to hierarchical superstructures. The synthesis procedure has great potential in efficient nanomanufacturing as it can achieve scalable production of the above shapes in a wide range of sizes, with minimum infrastructure and process requirements and little maintenance of the equipment

Interactions between bacterial surfaces and milk proteins, impact on food emulsions stability

Bacteria possess physicochemical surface properties such as hydrophobicity, Lewis acid/base and charge which are involved in physicochemical interactions between cells and interfaces. Moreover, food matrices are complex and heterogeneous media, with a microstructure depending on interactions between the components in media (van der Waals, electrostatic or structural forces, etc.). Despite the presence of bacteria in fermented products, few works have investigated how bacteria interact with other food components. The objective of the present study was to determine the effects of the surface properties of lactic acid bacteria on the stability of model food emulsions. The bacteria were added to oil/water emulsions stabilized by milk proteins (sodium caseinate, whey proteins concentrate or whey proteins isolate) at different pH (from 3 to 7.5). The effect of bacteria on the emulsions stability depended on the surface properties of strains and also on the characteristics of emulsions. Flocculation and aggregation phenomena were observed in emulsion at pHs for which the bacterial surface charge was opposed to the one of the proteins. The effects of bacteria on the stability of emulsion depended also on the concentration of cations present in media such as Ca2+. These results show that the bacteria through their surface properties could interact with other compounds in matrices, consequently affecting the stability of emulsions. The knowledge and choice of bacteria depending on their surface properties could be one of the important factors to control the stability of matrices such as fermentation media or fermented products.Région Bourgogne, Agence Universitaire de la Francophonie

Numerical simulations of complex fluid-fluid interface dynamics

Interfaces between two fluids are ubiquitous and of special importance for industrial applications, e.g., stabilisation of emulsions. The dynamics of fluid-fluid interfaces is difficult to study because these interfaces are usually deformable and their shapes are not known a priori. Since experiments do not provide access to all observables of interest, computer simulations pose attractive alternatives to gain insight into the physics of interfaces. In the present article, we restrict ourselves to systems with dimensions comparable to the lateral interface extensions. We provide a critical discussion of three numerical schemes coupled to the lattice Boltzmann method as a solver for the hydrodynamics of the problem: (a) the immersed boundary method for the simulation of vesicles and capsules, the Shan-Chen pseudopotential approach for multi-component fluids in combination with (b) an additional advection-diffusion component for surfactant modelling and (c) a molecular dynamics algorithm for the simulation of nanoparticles acting as emulsifiers.Comment: 24 pages, 12 figure

Self-shaping of oil droplets via the formation of intermediate rotator phases upon cooling.

Revealing the chemical and physical mechanisms underlying symmetry breaking and shape transformations is key to understanding morphogenesis. If we are to synthesize artificial structures with similar control and complexity to biological systems, we need energy- and material-efficient bottom-up processes to create building blocks of various shapes that can further assemble into hierarchical structures. Lithographic top-down processing allows a high level of structural control in microparticle production but at the expense of limited productivity. Conversely, bottom-up particle syntheses have higher material and energy efficiency, but are more limited in the shapes achievable. Linear hydrocarbons are known to pass through a series of metastable plastic rotator phases before freezing. Here we show that by using appropriate cooling protocols, we can harness these phase transitions to control the deformation of liquid hydrocarbon droplets and then freeze them into solid particles, permanently preserving their shape. Upon cooling, the droplets spontaneously break their shape symmetry several times, morphing through a series of complex regular shapes owing to the internal phase-transition processes. In this way we produce particles including micrometre-sized octahedra, various polygonal platelets, O-shapes, and fibres of submicrometre diameter, which can be selectively frozen into the corresponding solid particles. This mechanism offers insights into achieving complex morphogenesis from a system with a minimal number of molecular components.European Research Council (Grant ID: EMATTER 280078), European networks COST MP 1106 and 1305 and the capacity building project BeyondEverest of the European Commission (Grant ID: 286205)This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1618

‘Everyday bordering’ in England, Sweden and Bulgaria: Social work decision-making processes when working with migrant family members

The global movement of people is a growing feature of contemporary life, and it is essential that professionals providing support services know how to best engage with migrant families. However, despite globalisation and the related processes of de-bordering, borders continue to remain significant and, in contemporary life, the ways in which immigration is controlled and surveilled—bureaucratically and symbolically—are multiple. The paper draws on data gathered in the immediate period following the so called 2015 European ‘migration crisis’ and examines whether and in what ways social workers in three European countries—Bulgaria, Sweden and England—enact bordering in their work with migrant family members. We apply the concept of ‘everyday bordering’ to the data set: whilst borders are traditionally physical and at the boundary between nation states, bordering practices increasingly permeate everyday life in bureaucratic and symbolic forms. Overall, the data show that everyday bordering affects social work practice in three ways: by social workers being required to engage in bordering as an everyday practice; by producing conditions that require social workers to negotiate borders; and in revealing aspects of symbolic everyday bordering. Our analyses shows that ‘everyday bordering’ practices are present in social work decision-making processes in each country, but the forms they take vary across contexts. Analysis also indicates that, in each country, social workers recognise the ways in which immigration control can impact on the families with whom they work but that they can also inadvertently contribute to the ‘othering’ of migrant populations

Mechanisms of Drug Solubilization by Polar Lipids in Biorelevant Media

Despite the widespread use of lipid excipients in both academic research and oral formulation development, rational selection guidelines are still missing. In the current study, we aimed to establish a link between the molecular structure of commonly used polar lipids and drug solubilization in biorelevant media. We studied the effect of 26 polar lipids of the fatty acid, phospholipid or monoglyceride type on the solubilization of fenofibrate in a two-stage in vitro GI tract model. The main trends were checked also with progesterone and danazol.Based on their fenofibrate solubilization efficiency, the polar lipids can be grouped in 3 main classes. Class 1 substances (n = 5) provide biggest enhancement of drug solubilization (>10-fold) and are composed only by unsaturated compounds. Class 2 materials (n = 10) have an intermediate effect (3-10 fold increase) and are composed primarily (80 %) of saturated compounds. Class 3 materials (n = 11) have very low or no effect on drug solubilization and are entirely composed of saturated compounds.The observed behaviour of the polar lipids was rationalized by using two classical physicochemical parameters: the acyl chain phase transition temperature (Tm) and the critical micellar concentration (CMC). Hence, the superior performance of class 1 polar lipids was explained by the double bonds in their acyl chains, which: (1) significantly decrease Tm, allowing these C18 lipids to form colloidal aggregates and (2) prevent tight packing of the molecules in the aggregates, resulting in bigger volume available for drug solubilization. Long-chain (C18) saturated polar lipids had no significant effect on drug solubilization because their Tm was much higher than the temperature of the experiment (T = 37 C) and, therefore, their association in colloidal aggregates was limited. On the other end of the spectrum, the short chain octanoic acid manifested a high CMC (50 mM), which had to be exceeded in order to enhance drug solubilization. When these two parameters were satisfied (C > CMC, Tm Texp), the increase of the polar lipid chain length increased the drug solubilization capacity (similarly to classical surfactants), due to the decreased CMC and bigger volume available for solubilization.The hydrophilic head group also has a dramatic impact on the drug solubilization enhancement, with polar lipids performance decreasing in the order: choline phospholipids > monoglycerides > fatty acids.As both the acyl chain length and the head group type are structural features of the polar lipids, and not of the solubilized drugs, the impact of Tm and CMC on solubilization by polar lipids should hold true for a wide variety of hydrophobic molecules. The obtained mechanistic insights can guide rational drug formulation development and thus support modern drug discovery pipelines.<br /

Solubilization of Itraconazole by Surfactants and Phospholipid-Surfactant Mixtures: Interplay of Amphiphile Structure, pH and Electrostatic Interactions

Although surfactants are frequently used in enabling formulations of poorly water-soluble drugs, the link between their structure and drug solubilization capacity is still unclear. We studied the solubilization of the “brick-dust” molecule itraconazole by 16 surfactants and 3 phospholipid:surfactant mixtures. NMR spectroscopy was used to study in more details the drug-surfactant interactions. Very high solubility of itraconazole (up to 3.6 g/L) was measured in anionic surfactant micelles at pH = 3, due to electrostatic attraction between the oppositely charged (at this pH) drug and surfactant molecules. 1H NMR spectroscopy showed that itraconazole is ionized at two sites (2+ charge) at these conditions: in the phenoxy-linked piperazine nitrogen and in the dioxolane-linked triazole ring. The increase of amphiphile hydrophobic chain length had a markedly different effect, depending on the amphiphile type: the solubilization capacity of single-chain surfactants increased, whereas a decrease was observed for double-chained surfactants (phosphatidylglycerols). The excellent correlation between the chain melting temperatures of phosphatidylglycerols and itraconazole solubilization illustrated the importance of hydrophobic chain mobility. This study provides rules for selection of itraconazole solubilizers among classical single-chain surfactants and phospholipids. The basic physics underpinning the described effects suggests that these rules should be transferrable to other “brick-dust” molecules