Nanoparticle surface decoration mediated efficient protein and peptide co-encapsulation with precise ratiometric control for self-regulated drug release

Accuratly controlling drug release from a smart "self-regulated" drug delivery system is still an ongoing challenge. Herein, we developed a surface decoration strategy to achieve an efficient drug encapsulation with precise ratiometric control. Thanks to the surface decoration with cationic carrier materials by electrostatic attraction, the surface properties of different protein and peptide nanoparticles were uniformed to those adsorbed carrier materials. These carrier materials endowed protein and peptide nanoparticles with good dispersity in the oil phase and significantly inhibited the drug transfer from oil to water. With uniform surface properties, we realized the co-encapsulation of multiple types of proteins and peptides with precise ratiometric control. The encapsulation efficiency was higher than 87.8% for insulin. After solidification, the adsorbed materials on the surface of nanoparticles formed a solid protection layer, which prolonged the mean residence time of insulin from 3.3 ± 0.1 h (for insulin solution) to 47.5 ± 1.3 h. In type 1 diabetes, the spermine-modified acetalated dextran microparticle co-loaded with insulin, glucose oxidase and catalase maintained the blood glucose level within the normal range for 7 days.