Dependence of the Core–Shell Structure on the Lipid Composition of Nanostructured Lipid Carriers: Implications for Drug Carrier Design

Nanostructured lipid carriers (NLCs) are a new generation of lipid vectors for drug delivery systems (DDSs), which are composed of solid and liquid lipids dispersed throughout the inner lipid matrix. This study provides molecular and physicochemical characterizations of the NLC core region. According to the fluorescence anisotropy analysis, NLCs might have a more rigid shell (high anisotropy) and a less rigid core (low anisotropy). Based on cryo-transmission electron microscopy (cryo-TEM) observations, most NLC particles had a spherical shape with a crystal-like lamellar structure that might have originated from the crystallized lipids. The NLC particles with a lower concentration of solid lipids exhibited a faceted structure formed by the crystal lattice in the outer region. This result was verified through differential scanning calorimetry (DSC), which confirmed a polymorphism of the solid lipid in NLCs. The crystal structure was confirmed by X-ray diffraction (XRD) peak intensities, which were influenced by the lipid composition. Furthermore, a linear correlation was observed between the solid lipid-to-total lipid ratio and the anisotropy gap (rgap), transition energy (ΔH), and crystallinity percentage. These parameters can be used to predict the existence of the shell, rigid state fraction, and crystals in the NLC structure. Lipid rigidity and structural heterogeneity are essential for dispersive stability and drug-loading properties. Therefore, by adjusting the lipid composition, an optimized design of NLCs with high efficacy can be achieved for DDSs.