Design and manufacture of lipid particles for emulsion stabilisation

Much of our everyday nutrition is based on foods that are emulsions or have been emulsified at a certain stage during their processing. Emulsions’ inherent metastable state urges the introduction of emulsifiers, as a physical barrier that prevents droplets from coming together. In lieu of this approach, Pickering emulsions (i.e. droplets stabilised by solid particles) have amassed a great deal of both theoretical and commercial interest due to their scope of added functionalities. These include an exceptionally high stability and the compliance with the current demand for/appeal of formulations based on natural ingredients. Yet, their large scale adoption by the food industry has been hampered by the lack of a reservoir of edible structures that can be used as Pickering stabilisers. This thesis suggests the use of particles made of lipids as an alternative option for the design of Pickering-type emulsion stabilisers. Colloidal crystalline structures were fabricated via a melt-emulsification and subsequent crystallisation route. Solid particle characteristics, crucial for Pickering stabilisation (e.g. size, interfacial behaviour), could be controlled by adjustments to formulation and processing parameters. Building upon the knowledge gained from this initial study, colloidal lipid particles were assessed for their effectiveness to act as emulsifiers in oil-in-water (o/w) emulsions and also, for their aptitude to undergo a dehydration and rehydration process without variation of dimension or Pickering functionality

Solid lipid nanoparticles and nanostructured lipid carriers of dual functionality at emulsion interfaces. Part II:active carrying/delivery functionality

The utilisation of lipid nanostructures that can in tandem act as Pickering emulsion stabilisers and as active carrier/delivery systems, could potentially enable the development of liquid (emulsion-based) formulations with the capacity for multi-active encapsulation and delivery. Part I of this work focused on the first aspect of this two-fold functionality by investigating the capacity of both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) to act as effective Pickering particles in o/w emulsions. Herein, attention shifts to the secondary functionality, with part II of this study assessing both SLNs and NLCs in terms of their capacity to act as carriers and release regulators for curcumin, a model hydrophobic active. The previously established Pickering functionality and physical properties in terms of particle size, zeta potential and interfacial tension of the lipid particles remained unaffected after encapsulation of curcumin. In emulsions, loss of crystalline (solid lipid) matter and particle interfacial presence were specifically investigated, as these aspects can impact upon the particles’ active carrying and delivery performance. Low solid matter losses were recorded for all emulsions (ranging between 0% and 15%), with increasing liquid lipid fraction in the particles (SLNs to NLCs) resulting in relatively higher depletion of crystallinity. Removal of unadsorbed surfactant (remnant from the particle formation processing step) prior to emulsification led to higher particle interfacial occupancy. Despite said changes, the lipid particles’ curcumin carrying capacity, expressed as encapsulation efficiency and loading capacity, did not differ between an emulsion and dispersion setting. Although the active carrying capacity was retained, it was shown that the presence of the particles at the emulsion interfaces affects the curcumin release rate. Partial migration of curcumin to the oil droplet and creation of an additional release-inducing potential to the particles in close proximity to the droplet interface are proposed to be responsible for the overall faster active expulsion. What is more, the curcumin release profile from either SLNs or NLCs (also) stabilising an emulsion microstructure, was shown to persist after storage; either storage of the particles (up to 4 months) prior to emulsification, or storage of emulsions (up to 3 months) stabilised by ‘freshly’ formed lipid particles. Overall, the present study provides evidence that the two-fold functionality of the lipid particles can be indeed realised, markedly demonstrating that their concurrency does not compromise one another

Solid lipid nanoparticles and nanostructured lipid carriers of dual functionality at emulsion interfaces. Part I : Pickering stabilisation functionality

Solid lipid nanoparticles and nanostructured lipid carriers are two types of lipid nanoparticulate systems, that have been primarily studied for their capability to function as active carriers, and only more recently utilised in Pickering emulsion stabilisation. Unveiling the factors that impact upon the lipid particle characteristics related to their Pickering functionality could enable the development of a liquid formulation with tailored microstructure and potentially the capacity to display a two-fold performance. In part I, this work investigates how certain formulation characteristics, namely solid-to-liquid lipid mass ratio and presence of unadsorbed surfactant in the aqueous carrier phase, affect the structural properties of the lipid particles, and in turn how these influence their Pickering stabilisation capacity. The effect of the formulation parameters was assessed in terms of the wettability and physicochemical properties of the lipid particles, including particle size, crystallinity and interfacial behaviour. Lipid particles fabricated with higher liquid lipid content (70% w/w) were shown to be more hydrophilic and have lower surfactant decoration at their surface compared to particles containing lower or no liquid lipid in their crystalline matrix. The emulsion stabilisation ability through a Pickering mechanism was confirmed for all types of lipid particles using polarised microscopy. Increasing liquid lipid content and removal of excess surfactant did not compromise the particle stabilisation capacity, though emulsion droplets of larger sizes were initially acquired in the latter case. The particle-stabilised emulsions maintained their physical integrity, with particles retaining close association with the emulsion interface over a storage period of 12 weeks

Design and manufacture of lipid particles for emulsion stabilisation

Much of our everyday nutrition is based on foods that are emulsions or have been emulsified at a certain stage during their processing. Emulsions’ inherent metastable state urges the introduction of emulsifiers, as a physical barrier that prevents droplets from coming together. In lieu of this approach, Pickering emulsions (i.e. droplets stabilised by solid particles) have amassed a great deal of both theoretical and commercial interest due to their scope of added functionalities. These include an exceptionally high stability and the compliance with the current demand for/appeal of formulations based on natural ingredients. Yet, their large scale adoption by the food industry has been hampered by the lack of a reservoir of edible structures that can be used as Pickering stabilisers. This thesis suggests the use of particles made of lipids as an alternative option for the design of Pickering-type emulsion stabilisers. Colloidal crystalline structures were fabricated via a melt-emulsification and subsequent crystallisation route. Solid particle characteristics, crucial for Pickering stabilisation (e.g. size, interfacial behaviour), could be controlled by adjustments to formulation and processing parameters. Building upon the knowledge gained from this initial study, colloidal lipid particles were assessed for their effectiveness to act as emulsifiers in oil-in-water (o/w) emulsions and also, for their aptitude to undergo a dehydration and rehydration process without variation of dimension or Pickering functionality

Formulation design, production and characterisation of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the encapsulation of a model hydrophobic active

Lipid nanoparticles have been widely investigated for their use as either carriers for poorly water soluble actives or as (Pickering) emulsion stabilisers. Recent studies have suggested that the fabrication of lipid nanostructures that can display both these performances concurrently, can enable the development of liquid formulations for multi-active encapsulation and release. Understanding the effects of different formulation variables on the microstructural attributes that underline both these functionalities is crucial in developing such lipid nanostructures. In this study, two types of lipid-based nanoparticles, solid lipid nanoparticles and nanostructured lipid carriers, were fabricated using varying formulation parameters, namely type of solid lipid, concentration of liquid lipid and type/concentration of surface active species. The impact of these formulation parameters on the size, thermal properties, encapsulation efficiency, loading capacity and long-term storage stability of the developed lipid systems, was studied. Preliminary lipid screening and processing conditions studies, focused on creating a suitable lipid host matrix of appropriate dimensions that could enable the high loading of a model hydrophobic active (curcumin). Informed by this, selected lipid nanostructures were then produced. These were characterised by encapsulation efficiency and loading capacity values as high as 99% and 5%, respectively, and particle dimensions within the desirable size range (100-200 nm) required to enable Pickering functionality. Compatibility between the lipid matrix components, and liquid lipid/active addition were shown to greatly influence the polymorphism/crystallinity of the fabricated particles, with the latter demonstrating a liquid lipid concentration-dependent behaviour. Successful long-term storage stability of up to 28 weeks was confirmed for certain formulations