Solid lipid nanoparticles and nanoemulsions with solid shell: Physical and thermal stability

Abstract

Hypothesis: Nanoemulsions (NE) and solid lipid nanoparticles (SLN) used for drug delivery should have a solid shell to be stable during long shelf life and become liquid at human body temperature. The core components of lipid nanoparticles can be partially incorporated into the shell and affect the physical and thermal stability.

Experiments: We prepared NE and SLN by the phase inversion temperature (PIT) method. Solidification of the surfactants Tween60 and Span 60 on the surface of NE droplets with paraffin oil resulted in the formation of the solid shell. SLN contained stearic acid in the core and the same surfactants in the solid shell. The size, structure and stability of the NE and SLN were studied by DLS and cryo-TEM. Their crystallization and melting were analyzed using DSC.

Findings: The lipid nanoparticles were resistant to aggregation and sedimentation and hold up to at least two cycles of heating to 50-60 °C and subsequent cooling to 5 °C, even though the upper temperatures were higher than the melting point of the surfactant shell. The expected liquid core/solid shell morphology of NE was confirmed. SLN were composed of a semi-liquid core of supercooled stearic acid melt and coated with a solid surfactant shell, so they can be treated as NE. Stearic acid molecules penetrated the shell, leading to an increase in its melting point.

Keywords: Lipid crystallization; Nanoemulsion; Solid lipid nanoparticle; Span 60; Stearic acid; Tween 60; cryo-TEM.