Emulsion microgel particles: from design to oral to gastrointestinal digestion

Lipophilic active molecules, such as fat soluble vitamins, flavourings and fatty acids pose challenges for their application in food matrices due their water-insolubility, rapid oxidation and degradation during physiological transit. Based on the perceived knowledge gap from the literature review, a novel encapsulation strategy, targeting the delivery of lipophilic molecules, was developed in this thesis: emulsion microgel particles. These engineered smart particles are soft gel like particles encapsulating several oil droplets. These particles can alter their network structure, swelling behaviour, permeability or mechanical strength in response to internal physiological stimuli (e.g., change in pH, ionic strength, temperature, mechanical shear, enzymatic action, etc.). By investigating the nature of two specific biopolymer networks (i.e., starch gel or whey protein gel) and the interactions between the filler (i.e., emulsion droplets) and the matrix (i.e., the gel), two different approaches (top-down or bottom-up) were used to design these emulsion microgel particles. The unique design of the emulsion microgel particles developed in this PhD was that both the emulsifying agent and the matrix material were composed of the same biopolymer without the need of additional hydrocolloids. The characterization techniques used in this thesis included particle sizing, microscopy at various length scales, zeta-potential, rheology, tribology, sodium dodecyl sulphate polyacrylamide gel electrophoresis, pH-stat titrimetric measurements supported by theoretical calculations. In view of the above, the rheological properties and microstructural breakdown of the model emulsion gels were first analysed. The oil content, particle size, filler to matrix ratio and matrix polymer properties were also examined. Emphasis was then placed on the different response mechanisms of the starch- or whey protein-based emulsion microgel particles when subjected to different environmental stresses, such as acidic pH, enzyme activity (α-amylase for oral relevance, pepsin or trypsin for gastrointestinal relevance) and mechanical shear. Successfully, the emulsion microgel particles contributed to the improvement of food based delivery systems for lipophilic materials. Starch-based emulsion microgel particles were found to be suitable for the protection of lipophilic molecules against oral shear and coalescence whilst providing appropriate lubrication via both enzyme and shear-response mechanism. Whey protein-based emulsion microgel particles were established to protect the lipophilic molecules from harsh gastric environment whilst enabling complete release of free fatty acid during the intestinal phase due to both enzyme and pH-assisted mechanisms. The findings from this PhD thesis thus provide guidelines to develop new bio-responsive materials where these emulsion microgel particles can be used to offer excellent site-dependent controlled release properties for lipophilic materials

Scalloped pattern deposition during the spreading and drying of polymer droplets.

Droplets containing polyvinylpyrrolidone (PVP) dissolved in ethanol display a distinctive scalloped pattern at the rim while spreading and drying on a high-energy surface. Two distinct spreading regimes are observed, leading to the formation of a thin film with a uniform height that extends from the original droplet. An experimental study indicates polymer accumulation at the edge containing trace water, resulting in a surface tension gradient across the droplet, enhancing the droplet's spreading. This fast-spreading film develops a ridge at the contact line and becomes unstable. The influence of evaporation within the droplet shows no significant effect on the wavelength of the instability. Instead, the magnitude of the surface tension gradient and the surface energy of the substrate emerge as the dominant factors influencing the instability. This observation is validated by saturating the environment surrounding the droplet with ethanol vapour to reduce evaporation or employing solvents with low vapour pressure. Additionally, PVP in ethanol droplets deposited on hydrophobic substrates demonstrate a stable and pinned contact line, contrasting the behaviour observed on high-energy surfaces. By identifying the critical overlap concentration of the polymer, the transitional threshold between the scalloped instability and ringlike morphology is determined. The scalloped instability can be suppressed by removing residual water from the solution, eliminating the surface tension gradient, indicating that Marangoni forces are the underlying cause of the observed instability. The long-wave evolution equation, assuming a constant Marangoni shear flow, accurately predicts the most unstable wavelength, demonstrating good agreement with experimental observations.ICase award from EPSRC ICase award from Unileve

Liquid-Liquid Phase Separation Induced by Vapor Transfer in Evaporative Binary Sessile Droplets.

Drying of binary sessile droplets consisting of ethanol and octamethyltrisiloxane on a high-energy surface is investigated. During the process of evaporation, the droplets undergo liquid-liquid phase separation, resulting in the appearance of microdroplets at the liquid-air interface, which subsequently violently burst. This phase separation is attributed to water vapor transfer into the droplet, which modifies the solubility and leads to the formation of a ternary mixture. The newly formed ternary mixture may undergo nucleation and growth or spinodal decomposition, depending on the droplet composition path. By control of the relative humidity of air, phase separation can be mitigated or even eliminated. The droplets also display high mobility and complex wetting behavior due to phase separation, with two contracting and two spreading stages. The mass loss experiments reveal that the droplets undergo three distinct drying stages with an enhanced evaporation rate observed during the phase separation stage. A modified diffusion-limited model was employed to predict the evaporation rate, accounting for the physiochemical changes during evaporation and proved to be consistent with experimental observations. The findings of this work enhance our understanding of a coupled fundamental process involving the evaporation of multicomponent mixtures, wetting, and phase separation.ICase award from EPSRC and Unileve

Scalloped pattern deposition during the spreading and drying of polymer droplets †

Acknowledgements: This work has been funded by the Engineering and Physical Sciences Research Council (EPSRC), and CASE studentship funding from Unilever UK.Droplets containing polyvinylpyrrolidone (PVP) dissolved in ethanol display a distinctive scalloped pattern at the rim while spreading and drying on a high-energy surface. Two distinct spreading regimes are observed, leading to the formation of a thin film with a uniform height that extends from the original droplet. An experimental study indicates polymer accumulation at the edge containing trace water, resulting in a surface tension gradient across the droplet, enhancing the droplet's spreading. This fast-spreading film develops a ridge at the contact line and becomes unstable. The influence of evaporation within the droplet shows no significant effect on the wavelength of the instability. Instead, the magnitude of the surface tension gradient and the surface energy of the substrate emerge as the dominant factors influencing the instability. This observation is validated by saturating the environment surrounding the droplet with ethanol vapour to reduce evaporation or employing solvents with low vapour pressure. Additionally, PVP in ethanol droplets deposited on hydrophobic substrates demonstrate a stable and pinned contact line, contrasting the behaviour observed on high-energy surfaces. By identifying the critical overlap concentration of the polymer, the transitional threshold between the scalloped instability and ringlike morphology is determined. The scalloped instability can be suppressed by removing residual water from the solution, eliminating the surface tension gradient, indicating that Marangoni forces are the underlying cause of the observed instability. The long-wave evolution equation, assuming a constant Marangoni shear flow, accurately predicts the most unstable wavelength, demonstrating good agreement with experimental observations

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PAM, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and pArg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM(-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Two-particle transverse momentum correlations in pp and p-Pb collisions at LHC energies

Two-particle transverse momentum differential correlators, recently measured in Pb-Pb collisions at LHC energies, provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb--Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at $\sqrt{s} = 7$ TeV and $\sqrt{s_{\rm NN}} = 5.02$ TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p-Pb to Pb-Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.Two-particle transverse momentum differential correlators, recently measured in Pb--Pb collisions at energies available at the CERN Large Hadron Collider (LHC), provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at $\sqrt{s} = 7$ TeV and $\sqrt{s_{\rm NN}} = 5.02$ TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p--Pb to Pb--Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.Two-particle transverse momentum differential correlators, recently measured in Pb-Pb collisions at energies available at the CERN Large Hadron Collider (LHC), provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behavior. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at s=7TeV and sNN=5.02TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p-Pb to Pb-Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed

First measurement of Λc+\Lambda_\mathrm{c}^{+} production down to pT=0p_\mathrm{T} = 0 in pp and p-Pb collisions at sNN=5.02\sqrt{s_\mathrm{NN}} = 5.02 TeV

The production of prompt ${\mathrm {\Lambda_{c}^{+}}}$ baryons has been measured at midrapidity in the transverse momentum interval 0 Λc+ baryons has been measured at midrapidity in the transverse momentum interval 0<pT<1 GeV/c for the first time, in pp and p–Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=5.02TeV. The measurement was performed in the decay channel Λc+→pKS0 by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT-integrated Λc+ production cross sections in both collision systems were determined and used along with the measured yields in Pb–Pb collisions to compute the pT-integrated nuclear modification factors RpPb and RAA of Λc+ baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Λc+/D0 baryon-to-meson yield ratio is reported for pp and p–Pb collisions. Comparisons with models that include modified hadronization processes are presented, and the implications of the results on the understanding of charm hadronization in hadronic collisions are discussed. A significant (3.7σ) modification of the mean transverse momentum of Λc+ baryons is seen in p–Pb collisions with respect to pp collisions, while the pT-integrated Λc+/D0 yield ratio was found to be consistent between the two collision systems within the uncertainties.The production of prompt \mathrm {\Lambda_{c}^{+}}$baryons has been measured at midrapidity in the transverse momentum interval$0<p_{\rm T}<1$GeV/$c$for the first time, in pp and p-Pb collisions at a centre-of-mass energy per nucleon-nucleon collision$\sqrt{s_\mathrm{NN}} = 5.02$TeV. The measurement was performed in the decay channel${\rm \Lambda_{c}^{+}\to p K^{0}_{S}}$by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The$p_{\rm T}$-integrated$\mathrm {\Lambda_{c}^{+}}$production cross sections in both collision systems were determined and used along with the measured yields in Pb-Pb collisions to compute the$p_{\rm T}$-integrated nuclear modification factors$R_{\rm pPb}$and$R_\mathrm{AA}$of$\mathrm{\Lambda_{c}^{+}}$baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The$\mathrm{\Lambda_{c}^{+}/D^0}$baryon-to-meson yield ratio is reported for pp and p-Pb collisions. Comparisons with models that include modified hadronisation processes are presented, and the implications of the results on the understanding of charm hadronisation in hadronic collisions are discussed. A significant ($3.7\sigma$) modification of the mean transverse momentum of$\mathrm {\Lambda_{c}^{+}}$baryons is seen in p-Pb collisions with respect to pp collisions, while the$p_{\rm T}$-integrated$\mathrm{\Lambda_{c}^{+}/D^0}$ yield ratio was found to be consistent between the two collision systems within the uncertainties