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

Abstract

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.

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

“…Therefore, there is clear indication that DMP release in the current systems is not limited by diffusion (Table S2 & Figure S3). Instead, applying the interfacial barrier-limited model to the DMP release profile gave an interfacial rate constant (kI) of 3.09 × 10 -12 cm 2 s -1 , which is slightly higher but comparable to the value reported for DMP-loaded o/w Pickering emulsions stabilised by NaCaS/CS co-precipitates, which also followed an interfacial barrier controlled release [19], in addition to other literature on the release of hydrophobic actives from emulsions [40,43]. It is therefore evident, that the SNL2 fabricated in the presence of WPI offer a significant barrier for the passage of DMP into the external phase (Figure 3B).…”

“…The present proof-of-principle work aims to demonstrate that the approach of Spyropoulos et al [19] can be successfully applied to emulsions stabilised by solid lipid nanoparticles (SLNs). SLNs have been extensively utilised as single-and multi-drug delivery systems for actives with different characteristics [20][21][22], but also investigated for their capacity to stabilise (Pickering) emulsions [23][24][25][26].…”

“…Dual release was achieved, with high encapsulation efficiencies for the two hydrophobic compounds, while for the combination of hydrophilic/hydrophobic compounds, the double emulsion method yielded the highest encapsulation efficiency. In another study [19], sodium caseinate/chitosan (NaCAS/CS, protein/polysaccharide) co-precipitated complexes (containing a hydrophilic active) were used to stabilise oil-in-water emulsion droplets (containing a secondary hydrophobic active). This approach enabled the segregated co-encapsulation and independent co-release of two incompatible actives from a simple emulsion microstructure.…”

Food biotechnology

“…lipid digestion [29]. However, with knowledge of physical stability of microstructures Spyropoulos et al [44] have developed the ability for multi-active deliver from simple O/W emulsions.…”

Emulsifiers of Pickering-like characteristics at fluid interfaces: Impact on oil-in-water emulsion stability and interfacial transfer rate kinetics for the release of a hydrophobic model active

“…This may be employed to increase active stability, taste masking (e.g. peptide bitterness) [2], control delivery rates to biological targets, and/or to co-formulate otherwise physically disparate actives within the same liquid formulation [3], [4].…”