Surfactant-driven modulation of protein corona on solid lipid nanoparticles: Insights including molecular docking...

Nanoparticles have been used in nanomedicine for therapeutic purposes. Lipids have been a popular choice of material in the synthesis of biocompatible nanoparticles due to their ability to encapsulate diverse therapeutic agents. However, once introduced into biological environments, nanoparticles rapidly adsorb proteins on their surface, forming a protein corona that can alter drug release, targeting and cellular interactions. Understanding these effects is essential for optimizing solid lipid nanoparticles (SLNs) as drug delivery systems.

SLNs were synthesized using stearic acid (SA) as the lipid core and stabilized with surfactants, Tween 80 and SDS (sodium dodecyl sulphate). To mimic in vitro conditions, SLNs were incubated with 5% FBS (foetal bovine serum) for varying durations to allow soft and hard protein corona formation. SLNs were characterized for size and surface charge via dynamic light scattering while UV visible spectroscopy, protein adsorption studies, FTIR and the Bradford Assay were employed to confirm and quantify protein corona formation. In parallel, molecular docking was conducted to analyse protein-nanoparticle interactions. To investigate the potential influence of protein corona formation on drug release, ceftriaxone (CTX) was encapsulated within SLNs followed by immediate incubation to allow corona formation. Subsequent evaluations included drug leakage, release profile and antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa.

Protein adsorption was confirmed on all SLN formulations and closely correlated with nanoparticle surface charge. Formulations with more negative zeta potentials adsorbed higher amounts of protein. SDS concentration influenced protein adsorption with higher SDS content reducing overall corona formation. Molecular docking revealed that protein-ligand interactions were maintained by hydrogen bonding and hydrophobic forces. Drug release studies confirmed that the protein corona reduced cumulative drug release by 6%. Antibacterial assays confirmed slightly reduced efficacy against both strains aligning with the reduced cumulative drug release.

This study demonstrated that protein corona formation on dual-surfactant SLNs is strongly influenced by surface charge and surfactant composition and in turn modulates drug release dynamics. The protein corona was shown to modulate drug release with potential implications for antibacterial efficacy. These findings highlight the importance of tailoring surface properties to control protein-nanoparticle interactions thus providing insight into the design of lipid-based nanoparticles for therapeutic applications.