Pickering emulsion-based encapsulation strategies for delivery of curcumin

Curcumin is a potent bioactive polyphenolic compound but its bioavailability when orally administered is limited because of its low solubility in aqueous environments and chemical/ metabolic degradation during gastrointestinal transit. Oil-in-water emulsions have been extensively used as delivery systems for curcumin to target physiological sites. Particularly, emulsions stabilized by solid particles, also known as Pickering emulsions, have gained remarkable research interest as delivery vehicles due to their exceptional resistance to coalescence over prolonged periods of time and the fact that these particles are not desorbed by intestinal biosurfactants (bile salts) because of their high detachment energies. This thesis focuses on the design of complex particulate Pickering interfaces using two types of interactions (i.e. electrostatic and covalent) between whey protein and polysaccharides (dextran sulphate or dextran). Hence, three different Pickering emulsions; whey protein isolate nanogel particle-stabilized (EWPN), dextran sulphate coated-whey protein isolate nanogel particle-stabilized (DxS-EWPN) and whey protein isolate-dextran conjugated (or Maillard) microgel particle-stabilized (EWPDxM) Pickering emulsions were created as delivery vehicles for curcumin. For EWPN, controlled retention of curcumin was associated with the effect of pH and ionic strength on the partitioning of curcumin between the oil phase and the nanogel particle-laden interface. Also, by using an in vitro gastric model, pepsin hydrolysis was restricted in DxS-EWPN compared to EWPN. In addition, Maillard conjugation was used to engineer novel conjugated microgel particles (WPDxM) that could stabilize Pickering emulsions (EWPDxM) that exhibited gastric-stable properties as opposed to non-conjugated systems. Finally, the bioaccessibility and cellular uptake of curcumin by Caco-2 cells in the three different Pickering interfaces was evaluated after in vitro digestion. All three systems offered similar bioaccessibility due to similar degree of free fatty acid release during in vitro intestinal digestion. Nevertheless, the uniqueness was that DxS-EWPN and EWPDxM had better cell viability and cellular internalization of curcumin in comparison to EWPN. In summary, findings from this PhD ranges from colloidal design of novel biocompatible Pickering emulsion-based delivery vehicles, to identifying the vehicles that offer optimized gastric stability of emulsions and cellular delivery of bioactives (curcumin). These insights can be used for rational design of functional foods, food supplements, and for oral pharmaceutical and cosmetic applications in the future

Flaxseed oleosomes: Responsiveness to physicochemical stresses, tribological shear and storage

This study aimed to extract oleosomes (OLs) from flaxseeds and assess their response to environmental conditions during storage (pH and ionic strengths), shear and tribological stresses. Our hypothesis was that a shear-induced instability will enable OLs to exhibit favourable lubrication performance. During storage, OLs exhibited resistance to droplet aggregation for up to 6 weeks owing to the proteins (3.5–152.8 kDa molecular weights) stabilizing the OL droplets. However, presence of divalent (Ca2+) ions induced destabilization with marked increase in droplet size (p < 0.05). OLs demonstrated shear thinning behaviour, displaying an order of magnitude higher viscosity than flaxseed oil (FSO) at low shear rates (<10 s−1). Strikingly, OLs mirrored the frictional profile of FSO regardless of entrainment speeds, due to droplet coalescence, validating the hypothesis. Such kinetic stability with shear-induced coalescing feature of OLs hold strong potential for future plant-based food development, particularly in achieving desired mouthfeel characteristics

Pickering Water‐in‐Oil Emulsions Stabilized Solely by Fat Crystals

Water-in-oil (W/O) emulsions have attracted heightened attention because of the ever-increasing interest in using non-calorific water to replace calorie-dense fat in food. However, designing clean-label and ultra-stable W/O emulsions is a longstanding challenge in colloid science. Herein, a novel, facile approach is introduced to designing cocoa butter (CB)-based crystals to stabilize Pickering W/O emulsions. Results using a combination of small- and wide-angle X-ray scattering and microscopy across length scales reveal that the fat crystals formed in an oleogel of CB with vegetable oil offer high stability to water droplets (up to 60% (v/v)) against coalescence and phase inversion, over storage for 7 months. Such extraordinary stability is attributed to the nanoplatelet-like CB crystals of βV polymorph located at the water–oil interface and to the inter-droplet fat crystal network formation, interlocking the water droplets. The increment in water volume fraction endows gel-like properties with the water droplets acting as “active fillers.” These newly designed Pickering W/O emulsions stabilized solely by fat crystals with unusual rigidity offer great promise for fabricating advanced functional materials in food, pharmaceutics, and cosmetic applications, where long-term stabilization of water droplets using sustainable particles is a necessity

Macromolecular design of folic acid functionalized amylopectin- albumin core-shell nanogels for improved physiological stability and colon cancer cell targeted delivery of curcumin

Nanogels have potential for encapsulating cancer therapeutics, yet their susceptibility to physiological degradation and lack of cellular specificity hinder their use as effective oral delivery vehicles. Herein, we engineered novel albumin-core with folic acid functionalized hyperbranched amylopectin shell-type nanogels, prepared through a two-step reaction and loaded with curcumin while the proteinaceous core was undergoing thermal gelation. The nanogels had a mean hydrodynamic diameter of ca. 90 nm and ζ-potential of ca. -24 mV. Encapsulation of curcumin within the nanogels was restored, up to ca. 0.05 mg mL-1, beyond which, a gradual increase in size and a decrease in ζ-potential was observed. The core-shell structures were resilient to in vitro physiological oral-gastrointestinal digestion owing to a liquid crystalline B- and V-type polymorphism in the polysaccharide shell, the latter being driven by the shell functionalization with folic acid. Additionally, these biocompatible nanogels restored stability of the encapsulated curcumin and exhibited augmented cellular uptake and retention specifically in folate receptor-positive HT29 human colon adenocarcinoma cells, inducing early-stage apoptosis. Novel insights from this study represent a promising platform for rational designing of future oral delivery systems that can surmount physiological barriers for delivering cancer therapeutics to colon cancer cells with improved stability and specificity

Pickering emulsion stabilized by protein nanogel particles for delivery of curcumin: Effects of pH and ionic strength on curcumin retention

This study aimed to design whey protein nanogel particles (WPN)-stabilized Pickering emulsion as a delivery vehicle for curcumin (CUR). Firstly, the effectiveness of WPN to stabilize medium chain triglyceride (MCT) oil was assessed using droplet sizing, microscopy across scales, surface coverage calculations and interfacial viscosity measurements. Then, the ability of this delivery vehicle to encapsulate CUR and the effects of pH and ionic strengths on the retention of CUR were investigated in an in vitro release model at 37 ○C. Results demonstrate that 1.0 wt% WPN was sufficient to create a monolayer of particles at the droplet surface resulting in ultra-stable droplets that were resistant to coalescence over a year. Addition of 500 μg/ mL of CUR did not result in any change in the droplet size of the Pickering emulsion droplets. The CUR was fully retained within the Pickering emulsions, which might be attributed to the nanometric size of the gaps (≅30 nm) at the interface that did not allow CUR to diffuse out into the release media. The partitioning of CUR to the dispersed phase was influenced by pH of the media. Increased binding affinities between CUR and WPN at the interface (binding affinity constant, Ka = 1 × 104 M−1) existed at pH 3.0 as compared to that at pH 7.0 (Ka = 6.67 × 101 M−1) owing to the electrostatic interactions between CUR and interfacial WPN in the former. Such binding affinities between CUR and interfacial WPN at pH 7.0 was further influenced by presence of ions

Recent advances in emulsion-based delivery approaches for curcumin: From encapsulation to bioaccessibility

Background Curcumin has been widely acknowledged for its health-promoting effects. However, its application is often limited by its poor water solubility and biochemical/structural degradation during physiological transit that restricts its bioavailability. Emulsion based approaches have attracted the most research attention to encapsulate curcumin and improve its stability, bioaccessibility and bioavailability. Scope and approach This review summarizes the recent advances in application of different oil-in-water emulsion-based approaches, such as, conventional emulsions (surfactants-, protein- and protein-polysaccharide-stabilized emulsions), nanoemulsions, and Pickering emulsions that have been specifically used to deliver curcumin. Particular emphasis is given to factors affecting curcumin solubility, change in crystalline structure of curcumin upon dispersion and encapsulation efficiency. Changes in the droplet size and emulsion stability during in vitro oral-to-gastrointestinal digestion are discussed, with clear focus on the bioaccessibility of the encapsulated curcumin. Key findings and conclusions Key factors that influence curcumin delivery include emulsion droplet size, oil composition, volume fraction, dispersion conditions of curcumin in the oil phase and the type of interfacial materials. Nanoemulsions have been the preferred choice for delivery of curcumin up to now. Although scarce in literature, emulsions stabilized by edible Pickering particles as shown by recent evidence are effective in protecting curcumin in an in vitro gastrointestinal setting due to their high coalescence stability. Further studies with emulsions stabilized by food-grade particles and accurate tracking of the physiological fate (in vitro to human trials) of different emulsion-based delivery vehicles are essential for rational designing of curcumin-rich functional foods with high bioaccessibility

Recent advances in design and stability of double emulsions: Trends in Pickering stabilization

There is an increased pressure on food manufacturers to design low calorie and low fat foods to address the global obesity crisis. Designing double emulsions (DEs) is a microstructural approach to incorporate water that appears as promising fat replacement strategy. However, these complex microstructures are thermodynamically unstable and a thorough understanding of the factors that determine the stability of DEs are required to tailor their functionality. This review provides an update on the main strategies used to stabilize DEs, focusing on the developments in the last five years. Emphasis is placed on the recent use of surfactants, combination of surfactants with gelling agents, particles, fat crystals, and/or coatings. Novel processing techniques were also reviewed, and one-step processing methodologies were particularly examined. We also briefly reviewed the rheological and tribological performance of DEs. Properties and stability of the DEs depend strongly on the formulation and fabrication technique (homogenization, phase inversion, microfluidics, 3D Printing etc). Fat crystal forming a shell around the droplets offers a promising strategy to prevent diffusion of the internal phase in DEs. Pickering stabilization has captured significant research attention, though DEs fabricated solely using particle-laden interfaces are limited. A combined approach of Pickering and bulk stabilization by gelling the aqueous phase appears as a promising strategy to improve stability of DE, which needs research attention. Future studies should focus on characterizing rheological and tribological performance of DEs and link them with mouthfeel perception to accelerate their use in food applications

Conjugate microgel-stabilized Pickering emulsions: Role in delaying gastric digestion

In this study, a new class of microgels called ‘conjugate microgels’ was designed, where whey protein isolate (WPI) was conjugated with dextran (Dx, 500 kDa) (WPI-Dx) via Maillard reaction before fabricating the microgel particles. Such microgel particles were assessed for their abilities to act as Pickering stabilizers for oil-in-water emulsions and also checked if they offered gastric stability to the Pickering emulsions during in vitro digestion against interfacial pepsinolysis. WPI-Dx conjugates were obtained by controlled dry heating (60 °C, 79% RH, 24–48 h incubation). Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and ortho-phthaldialdehyde (OPA) profile revealed that the degree of conjugation ranged from 11.6 to 28.1%. The WPI-Dx conjugates were re-dispersed and heat-treated to form heat-set gels with moduli ranging from ∼45 to 250 kPa. Microgel particles (hydrodynamic diameters of 130–150 nm, ζ-potentials of −4.5 to −8.0 mV) were created by controlled shearing of these heat-set gels. Interfacial shear rheology measurements and microscopic examination confirmed that conjugated microgel particles with lower degree of conjugation (WPDx10M) were effective as Pickering stabilizers. When present in an aqueous dispersion, WPDx10M had reduced the degree of gastric proteolysis (120–130 μM free NH2) as compared to non-conjugated counterparts (187–205 μM free NH2). When present at the droplet surface, cross-correlation image analysis revealed that WPDx10M was successful in delaying interfacial gastric proteolysis. Insights from this study suggest that conjugate microgel particles might be useful to design gastric-stable Pickering emulsions in the future for effective delivery of lipophilic compounds to the intestines

Can tribology be a tool to help tailor food for elderly population?

The rapidly ageing population requires food products that meet their specific physiological needs and have pleasurable sensory characteristics. Conventionally, rheology is used as a food formulation design tool that allow food bolus to be swallowed safely. Nevertheless, in the last few decades, there has been increased understanding of soft-tribology of thickeners and fabrication of biologically-relevant tribological set-ups. We discuss how this knowledge can offer a solid baseline to employ tribology as a design tool to tailor foods for the elderly population with various oral insufficiencies. In depth characterization of oral conditions of the elderly population is a necessary undertaking to fabricate tribology apparatus that better emulate in vivo conditions, to allow rational design of food products for this growing population

Can tribology be a tool to help tailor food for elderly population?

This review comes from a themed issue on Food Chemistry & Biochemistry.International audienceThe rapidly ageing population requires food products that meet their specific physiological needs and have pleasurable sensory characteristics. Conventionally, rheology is used as a food formulation design tool that allows food bolus to be swallowed safely. Nevertheless, in the last few decades, there has been increased understanding of soft tribology of thickeners and fabrication of biologically relevant tribological set-ups. We discuss how this knowledge can offer a solid baseline to employ tribology as a design tool to tailor foods for the elderly population with various oral insufficiencies. In-depth characterisation of oral conditions of the elderly population is a necessary undertaking to fabricate tribology apparatus that better emulates in vivo conditions, to allow rational design of food products for this growing population