Role of electrostatic interactions in protein loading in PLGA-PEG nanoparticles

Polymeric nanoparticles (NPs) are emerging as promising protein drug delivery carriers for both oral and parenteral methods of administration. Understanding the mechanism of protein loading is imperative for designing more efficient drug delivery systems. However, the process of protein loading and the resulting structure of the polymeric NPs remain unclear. In this study, insulin and poly (lactic-co-glycolic acid) - poly (ethylene glycol) (PLGA-PEG) NPs are used as model protein and polymeric drug delivery carrier, respectively. We show that electrostatic interactions between the protein drug and the polymer play a key role in mediating the formation of these NPs. It is also observed that majority of the protein molecules interact with the corona of the NPs instead of the core. These results provide a deeper insight into the formation of protein loaded polymeric NPs synthesized by the nanoprecipitation method, which can lead to the development of more efficient future protein drug delivery systems.