Efficient Strategy for Protein Drug Carrier Design for Insights into the Protein–Polyelectrolyte Interaction

The protein carrier and encapsulation system based on polyelectrolytes plays crucial roles in drug research and development. Traditional methods such as isothermal titration calorimetry and molecular dynamics simulation have illuminated parts of this complex relationship. However, they fall short of capturing the full picture of the interaction during the carrier's fabrication and protein loading dynamics. We propose a strategy in this article that combines ordered porous layer interferometry (OPLI) with electrophoretic light scattering (ELS) to study this interaction, effectively investigating the mechanism of polyelectrolyte-protein interaction and verifying it through charge measurement. The layer-by-layer assembly method was used to fabricate the polyelectrolyte complex (PEC) layer on both silica colloidal crystal (SCC) films and silica nanospheres. OPLI with the SCC film as the substrate was employed to investigate real-time interaction between PEC and proteins, while ELS determined the ζ-potential of the PEC layer and proteins to illustrate the interaction mechanism further. It was found that surface charge affects electrostatic adsorption at different pH values and numbers of polyelectrolyte layers. As the ζ-potential difference increased, protein adsorption on the PEC layer also increased significantly. Adjusting the pH value during protein loading can maximize the loading efficiency. In our strategy, we can transfer the in situ interface study of OPLI into a dispersed nanosphere system directly because the silica nanosphere can be the building block of the OPLI substrate while being the solid supporter for polyelectrolyte carriers. By combining OPLI and ELS, this work provides an efficient strategy for developing protein drug carriers based on polyelectrolytes.