Research Advances for Protein-Based Pickering Emulsions as Drug Delivery Systems.

Nanotechnologically engineered protein-based carriers have attracted considerable attention in the pharmaceutical field due to the advantages of superior biocompatibility, tunability and good emulsifying properties. Recently, protein-based Pickering emulsions (PPEs) systems with multi-level structures have been introduced as innovative colloidal delivery systems for advanced drug encapsulation, protection, delivery and controlled release. Natural source protein nanoparticles are promising candidates to provide a wide range of functional performances and interfacial properties in the preparation and stabilization of Pickering emulsions. Herein, this review summarizes the development of PPEs in drug delivery systems, focusing on the research progress concerning the aspects of protein particle preparation methods, formation mechanisms and rational design principles, emphasizing the relationship between protein particle structure and functional properties. To further understand the interfacial behavior in protein nanoparticle stabilized emulsion, the mesoscopic dissipative particle dynamics (DPD) simulations were discussed, which bridges the gaps between macroscopic time and length scales, as well as molecular-scale simulations on particles and oil/water interface systems. The structure-effect relationship between the tunable physicochemical properties of protein-based interface design, which leads to the effective loading, stimuli-responsiveness for the controlled release and multiple delivery, was then summarized. Finally, the opportunities and challenges for the future development of PPEs for drug delivery are discussed. This review aims to provide a reference for the further application of PPEs as advanced drug delivery systems.