Abstract
The advantage of using nonlamellar lipid liquid crystalline phases has been demonstrated in many applications, such as drug delivery, protein encapsulation and crystallisation. We have recently reported that a mixture of mono- and diglycerides is able to form sponge-like nanoparticles (L3-NPs) with large enough aqueous pores to encapsulate macromolecules such as proteins. Here we use small angle neutron scattering (SANS) to reveal morphology, structural and chemical composition of these polysorbate 80 (P80) stabilized sponge phase nanoparticles, not previously known. Our results suggest that L3-NPs have a core-shell sphere structure, with a shell rich in P80. It was also found that even if P80 is mostly located on the surface, it also contributes to the formation of the inner sponge phase structure. An important aspect for the application and colloidal stability of these particles is their interfacial properties. Therefore, the interfacial behaviour of the nanoparticles on hydrophilic silica was revealed by Quartz crystal microbalance with dissipation (QCM-D) and neutron reflectivity (NR). Adsorption experiments reveal the formation of a thin lipid layer, with the dimension corresponding to a lipid bilayer after L3-NPs are in contact with hydrophilic silica. This suggests that the diglycerol monoleate/Capmul GMO-50/P80 particles reorganize themselves on this surface, probably due to interactions between P80 head group and SiO2.
Highlights
Uppsala University, Uppsala, Sweden e ISIS, STFC, Rutherford Appleton Laboratory, Didcot, UK f Camurus AB, Ideon Science Park, Lund, Sweden † Electronic supplementary information (ESI) available: Core–shell sphere model; estimated solvent volume fraction and scattering length density (SLD) of the lipid/polysorbate 80 (P80) of the core and shell and equations used for the calculation; Voigt viscoelastic model; shear and viscosity values obtained using the Voigt model; Quartz crystal microbalance with dissipation (QCM-D) results at different conditions; and neutron reflectometry fits for the 5-layer model
E-mail: tommy.nylander@fkem1.lu.se b NanoLund, Lund University, Lund, Sweden c Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden d Institut Laue Langevin, Grenoble, France and Department of Physics, Uppsala University, Uppsala, Sweden e ISIS, STFC, Rutherford Appleton Laboratory, Didcot, UK f Camurus AB, Ideon Science Park, Lund, Sweden † Electronic supplementary information (ESI) available: Core–shell sphere model; estimated solvent volume fraction and SLD of the lipid/P80 of the core and shell and equations used for the calculation; Voigt viscoelastic model; shear and viscosity values obtained using the Voigt model; QCM-D results at different conditions; and neutron reflectometry fits for the 5-layer model
A stock solution composed of Diglycerol monooleate (DGMO), glycerol monolein (GMO)-50 and P80 was first prepared by co-melting GMO-50 and P80 at 40 1C followed by further weighting of each component into a glass vial
Summary
Most of the LCNP investigated so far had inverse cubic or hexagonal inner structures. Vandoolaeghe et al.[19,23] studied the adsorption of glycerol monolein (GMO)/ pluronic F127 cubosomes on hydrophilic and hydrophobic silica at different conditions. It has been proposed earlier that P80 acts as a dispersing agent found on the outside of the particles, and contributes to the inner structure organization of the nonlamellar LCNP This effect is rather pronounced at high P80 concentrations, where even the loss of internal particle structure can occur.[22,25] In our earlier work[13] with the same DGMO/GMO-50/P80/water system as studied here, we were able to form nanoparticles with highly swollen sponge phase structures over a wider range than in the pure lipid–aqueous system. The results suggest that the L3-NPs, that were initially 180 nm in diameter, spread and rearrange into a thin lipid layer onto hydrophilic silica
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