Interaction of solid lipid nanoparticles with bovine serum albumin: physicochemical mechanistic insights.

This study investigates the interaction of solid lipid nanoparticles (SLNs) with the transport protein bovine serum albumin (BSA) in terms of thermodynamic signatures, employing both spectroscopic and calorimetric techniques. When nanoparticles are exposed to biological media, proteins are adsorbed on their surfaces, leading to protein corona formation. Therefore, controlling the formation of the protein corona is essential for therapeutic efficacy. Although SLNs have previously been explored solely as potential nano-carriers for drug delivery, no prior efforts have been made to study their interactions with biomolecules from a biophysical and mechanistic perspective. SLNs are colloidal dispersions of the solid lipid in an aqueous solution stabilized by surfactants. Herein, a hot emulsification methodology was employed to formulate SLNs, and their interactions with BSA were analyzed. The SLNs were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques to obtain information on their size, zeta potential, and shape. Fluorescence data suggested the presence of weak interactions between the SLNs and BSA. Static quenching is confirmed using time-correlated single-photon counting (TCSPC) experiments. Differential scanning calorimetric (DSC) and fluorescence spectroscopic experiments suggest the thermal stabilization of BSA by the SLNs. This stabilization results from the enhancement of the secondary structure of the protein without significantly altering the tertiary structure. Isothermal calorimetry (ITC) results suggest weak interactions between the SLNs and BSA, although not in a site-specific manner. Overall, mechanistic insights into lipid nanoparticle-protein interactions obtained from such studies efficiently overcome the hurdles associated with targeted drug delivery.