The role of lipid particle-laden interfaces in regulating the co-delivery of two hydrophobic actives from o/w emulsions

Abstract

Co-delivery strategies have become an integral active delivery approach, although understanding of how the microstructural characteristics could be deployed to achieve independently regulated active co-delivery profiles, is still an area at its infancy. Herein, the capacity to provide such control was explored by utilizing Pickering emulsions stabilized by lipid particles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These dual functional species, regarding their concurrent Pickering stabilization and active carrying/delivery capabilities, were formulated with different solid lipid and surfactant types, and the effect on the release and co-release modulation of two hydrophobic actives separately encapsulated within the lipid particles themselves and within the emulsion droplets was investigated. Disparities between the release profiles from the particles in aqueous dispersions or at an emulsion interface, were related to the specific lipid matrix composition. Particles composed of lipids with higher oil phase compatibility of the emulsion droplets were shown to exert less control over their release regulation ability, as were particles in the presence of surfactant micelles in the continuous phase. Irrespective of their formulation characteristics, all particles provided a level of active release control from within the emulsion droplets, which was dependant on the permeability of the formed interfacial layer. Specifically, use of a bulkier particle surfactant or particle sintering at the droplet interface resulted in more sustained droplet release rates. Compared to sole release, the co-release performance remained unaffected by the co-existence of the two hydrophobic actives with the co-release behavior persisting over a storage period of 1 month.

Keywords: Pickering emulsions; Solid lipid nanoparticles; co-encapsulation; co-release; interfacial sintering; nanostructured lipid carriers.

Graphical abstract

Figure 1.

In vitro release profile of curcumin-loaded SLN and NLC dispersions formulated with either Tween^® 80 (T80) as surfactant and different types of solid lipid (A) Compritol^® 888 ATO (C888) and (B) Precirol^® ATO 5 (P5), or different surface active species (C) Poloxamer 188 (P188) and C888 as solid lipid. NLCs were fabricated with Miglyol^® 812 as the liquid lipid, at 30% w/w of the total lipid phase mass. The release profile from a curcumin solution obtained under the same conditions is also depicted (a). The in vitro release kinetic Crank model (Eq. (3)) fitting of curcumin for each SLN (dashed line) and NLC (dotted line) dispersion is also presented. Graph A has been previously shown in (Sakellari et al., 2023) and is provided here for comparison purposes.

Figure 2.

DSC melting thermograms of SLN and NLC dispersions and their respective Pickering emulsions, for lipid particles formulated with either Tween^® 80 (T80) as surfactant and different types of solid lipid (A) Compritol^® 888 ATO (C888) and (B) Precirol^® ATO 5 (P5), or different surface active species (C) Poloxamer 188 (P188) and C888 as solid lipid. NLCs were fabricated with Miglyol^® 812 as the liquid lipid, at 30% w/w of the total lipid phase mass. The curves were normalized for the amount of solid matter present in each sample and shifted along the ordinate for better visualization. Graph A has been previously shown in literature (Sakellari et al., 2022, 2023) and is provided here for comparison purposes.

Figure 3.

Dynamic interfacial tension of aqueous dispersions of SLN and NLC formulations prepared with either Tween^® 80 (T80) as surfactant and different types of solid lipid (A) Compritol^® 888 ATO (C888) and (B) Precirol^® ATO 5 (P5), or different surface active species (C) Poloxamer 188 (P188) and C888 as solid lipid. NLCs were fabricated with Miglyol^® 812 as the liquid lipid, at 30% w/w of the total lipid phase mass. The curves of pure T80 and P188 solutions with similar concentration (1.2% w/w) as of those used for the dispersions are also presented for comparison. Data points are the average of three measurements and error bars represent the standard deviation. Graph A has been previously shown in (Sakellari et al., 2022) and is provided here for comparison purposes.

Figure 4.

Droplet size distribution of SLN- and NLC-stabilized emulsions, with lipid particles formulated with either Tween^® 80 (T80) as surfactant and different types of solid lipid (A) Compritol^® 888 ATO (C888) and (B) Precirol^® ATO 5 (P5), or different surface active species (C) Poloxamer 188 (P188) and C888 as solid lipid. NLCs were fabricated with Miglyol^® 812 as the liquid lipid, at 30% w/w of the total lipid phase mass. Graph A has been previously shown in (Sakellari et al., 2022) and is provided here for comparison purposes.

Figure 5.

Ratio of the melting enthalpies of the particles within an emulsion environment and those in a lipid particle dispersion setting (ΔH^T_em/ΔH_dis), representing the amount of crystalline material remaining within the emulsions stabilized by different types of lipid particles. Identical lowercase letters indicate no significant differences between samples.

Figure 6.

In vitro release profile of curcumin-loaded SLN- and NLC-stabilized emulsions formulated with either Tween^® 80 (T80) as surfactant and different types of solid lipid (A) Compritol^® 888 ATO (C888) and (B) Precirol^® ATO 5 (P5), or different surface active species (C) Poloxamer 188 (P188) and C888 as solid lipid. NLCs were fabricated with Miglyol^® 812 as the liquid lipid, at 30% w/w of the total lipid phase mass. The in vitro release kinetic Crank model (Eq. (3)) fitting of curcumin for each emulsion system stabilized by SLNs (dashed line) or NLCs (dotted line) is also presented. The release profile from a curcumin solution obtained under the same conditions (a) and that of the particles within the dispersion systems are also depicted in each respective graph. Graph A has been previously shown in the literature (Sakellari et al., 2023) and is provided here for comparison purposes.

Figure 7.

In vitro release profile of cinnamaldehyde-loaded emulsions stabilized with either Tween® 80 (T80) or Poloxamer 188 (P188) (a), droplet size distribution of the same systems (B). The release profile from a CA solution obtained under the same conditions is also depicted (a).

Figure 8.

In vitro release profile of cinnamaldehyde-loaded emulsions stabilized by SLNs and NLCs formulated with either Tween^® 80 (T80) as surfactant and different types of solid lipid (A) Compritol^® 888 ATO (C888) and (B) Precirol^® ATO 5 (P5), or different surface active species (C) Poloxamer 188 (P188) and C888 as solid lipid. NLCs were fabricated with Miglyol^® 812 as the liquid lipid, at 30% w/w of the total lipid phase mass. The interfacial barrier-limited model (Eq. (6)) fits to the data for the release of cinnamaldehyde from the SLN- (dashed line) and NLC- (dotted line) stabilized emulsions are also presented.

Figure 9.

DSC melting thermograms of C888/T80 SLN-stabilized emulsions before and after sintering at 64 and 78 °C for varying durations (a). The curves were normalized for the amount of solid matter present in each sample and shifted along the ordinate for better visualization. The melting curve of the C888/T80 SLN dispersion is also provided for comparison purposes. Ratio of the melting enthalpies (ΔH^T_em/ΔH_dis) of the emulsion systems presented in graph (a), representing the amount of crystalline material remaining within the emulsions post-processing (B). Identical lowercase letters indicate no significant differences between samples.

Figure 10.

Droplet size distribution of C888/T80 SLN-stabilized emulsions before and after thermal processing at 64 and 78 °C for 60 min (a). In vitro release profile of cinnamaldehyde-loaded emulsions stabilized by C888/T80-SLNs after being subjected to thermal processing at 64 °C for varying durations (B). The profile of the respective emulsion system prior-sintering is also presented for comparison purposes. The interfacial barrier-limited model (Eq. (6)) fits to the data for the release of cinnamaldehyde from each emulsion system is also presented (­ ­ no processing, ···· 64 °C 5 min,—64 °C 20 min, –⋅ 64 °C 60 min).

Figure 11.

In vitro co-release profiles of cinnamaldehyde-loaded emulsion droplets stabilized by curcumin-loaded C888/T80-SLNs measured immediately after preparation (A) and after 1 month of emulsion storage (B). Data are presented at longer (main graph) and shorter (inset graph) timescales to demonstrate differences in the release rates. The Crank model (Eq. (3)) fitting for all curcumin data (dotted lines) and the interfacial barrier-limited model (Eq. (6)) fitting for all cinnamaldehyde curves (dashed lines) are also presented. For comparison purposes, the single release profiles of curcumin-loaded C888/T80-SLN-stabilized (blank) emulsions and CA-loaded emulsions stabilized by blank C888/T80 SLNs are included in both graphs.