Independent co-delivery of model actives with different degrees of hydrophilicity from oil-in-water and water-in-oil emulsions stabilised by solid lipid particles via a Pickering mechanism: a-proof-of-principle study.

HYPOTHESIS: The development of vehicles for the co-encapsulation of actives with diverse characteristics and their subsequent controllable co-delivery is gaining increasing research interest. Predominantly centred around pharmaceutical applications, the majority of such co-delivery approaches have been focusing on solid formulations and less so on liquid-based systems. Simple emulsions can be designed to offer a liquid-based microstructural platform for the compartmentalised multi-delivery of actives. EXPERIMENTS: In this work, solid lipid nanoparticle stabilised Pickering emulsions were used for the co-encapsulation/co-delivery of two model actives with different degrees of hydrophilicity. Lipid particles containing a model hydrophobic active were prepared in the presence of either Tween 20 or whey protein isolate, and were then used to stabilise water-in-oil or oil-in-water emulsions, containing a secondary model active within their dispersed phase. FINDINGS: Solid lipid nanoparticles prepared with either type of emulsifier were able to provide stable emulsions. Release kinetic data fitting revealed that different co-delivery profiles can be achieved by controlling the surface properties of the lipid nanoparticles. The current proof-of-principle study presents preliminary data that confirm the potential of this approach to be utilised as a flexible liquid-based platform for the segregated co-encapsulation and independent co-release of different combinations of actives, either hydrophobic/hydrophilic or hydrophobic/hydrophobic, with diverse release profiles.

Fabrication and Utilization of Bifunctional Protein/Polysaccharide Coprecipitates for the Independent Codelivery of Two Model Actives from Simple Oil-in-Water Emulsions.

Aside from single active microencapsulation, there is growing interest in designing structures for the coencapsulation and codelivery of multiple species. Although currently achievable within solid systems, significant challenges exist in realizing such functionality in liquid formulations. The present study reports on a novel microstructural strategy that enables the coencapsulation and corelease of two actives from oil-in-water emulsions. This is realized through the fabrication of sodium caseinate/chitosan (NaCAS/CS) complexes that in tandem function as encapsulants of one active (hydrophilic) but also as ("Pickering-like") stabilizers to emulsion droplets containing a secondary active (hydrophobic). Confocal microscopy confirmed that the two coencapsulated actives occupied distinct emulsion microstructure regions; the hydrophilic active was associated with the NaCAS/CS complexes at the emulsion interface, while the hydrophobic active was present within the oil droplets. Aided by their segregated coencapsulation, the two actives exhibited markedly different corelease behaviors. The hydrophilic active exhibited triggered release that was promoted by changes to pH, which weakened the protein-polysaccharide electrostatic interactions, resulting in particle swelling. The hydrophobic secondary active exhibited sustained release that was impervious to pH and instead controlled by passage across the interfacial barrier. The employed microstructural approach can therefore lead to the segregated coencapsulation and independent corelease of two incompatible actives, thus offering promise for the development of liquid-emulsion-based formulations containing multiple actives.

Food-grade Pickering emulsions stabilised with solid lipid particles.

Aqueous dispersions of tripalmitin particles (with a minimum size of 130 nm) were produced, via a hot sonication method, with and without the addition of food-grade emulsifiers. Depending on their relative size and chemistry, the emulsifiers altered the properties of the fat particles (e.g. crystal form, dispersion state and surface properties) by two proposed mechanisms. Firstly, emulsifiers modify the rate and/or extent of polymorphic transitions, resulting in the formation of fat crystals with a range of polarities. Secondly, the adsorption of emulsifiers at the particle interface modifies crystal surface properties. Such emulsifier-modified fat particles were then used to stabilise emulsions. As the behaviour of these particles was predisposed by the kind of emulsifier employed for their manufacture, the resulting particles showed different preferences to which of the emulsion phases (oil or water) became the continuous one. The polarity of the fat particles decreased as follows: Whey Protein Isolate > Soy Lecithin > Soy Lecithin + Tween 20 > Tween 20 > Polyglycerol Polyricinoleate > no emulsifier. Consequently, particles stabilised with WPI formed oil-in-water emulsions (O/W); particles stabilised solely with lecithin produced a highly unstable W/O emulsion; and particles stabilised with a mixture of lecithin and Tween 20 gave a stable W/O emulsion with drop size up to 30 µm. Coalescence stable, oil-continuous emulsions (W/O) with drop sizes between 5 and 15 µm were produced when the tripalmitin particles were stabilised with solely with Tween 20, solely with polyglycerol polyricinoleate, or with no emulsifier at all. It is proposed that the stability of the latter three emulsions was additionally enhanced by sintering of fat particles at the oil-water interface, providing a mechanical barrier against coalescence.