Molecular interaction and localization of tocotrienol-rich fraction (TRF) within the matrices of lipid nanoparticles: Evidence studies by Differential Scanning Calorimetry (DSC) and Proton Nuclear Magnetic Resonance spectroscopy (1H NMR)

Nanostructured lipid carriers (NLCs), made from mixtures of solid and liquid lipids, were postulated to have superior properties over solid lipid nanoparticles (SLNs). Nonetheless, the architecture of their inner cores remains elusive. The objective of this study was to elucidate the mode by which tocotrienol-rich fraction (TRF) is entrapped within NLCs and the impact of TRF interaction with solid lipids on the long-term stability of the nanoparticles. The mode of TRF localization was postulated from TEM image analysis and 1H NMR signals’ amplitude. The size, polydispersity, and fusion enthalpy were found to decrease with an increase in TRF loading, which implied a distortion in the crystallinity of the nanoparticles and the preferential entrapment of TRF within the cores of the NLCs. Nonetheless, 1H NMR spectra of TRF-NLCs broadened as TRF load decreased from 100 to 10%, which was attributed to partial TRF mobility on the surface of the nanoparticles. This was confirmed by TEM images of NLCs at 50% TRF loads. These data led to the conclusion that NLCs have limited capacity to accommodate TRF with the excess being expelled to the surface of the nanoparticles. Such arrangement may have implication on future utility of the NLCs as drug delivery vehicles.