A Thin Polymer Layer Enables Peptide‐Polycation Complexes with Ultrahigh Efficient Encapsulation

Abstract A monolayer encapsulation is a new opportunity for engineering a system with high drug loading, but immobilizing polymer molecules on the surface of individual peptide nanoparticles is still an ongoing challenge. Herein, an individual peptide nanoparticle encapsulation strategy is proposed via surface adsorption, in which peptide molecules undergo granulation and subsequently aggregate with polymer molecules, forming a network via electrostatic interactions. Under the water phase, surplus polymer molecules dissolve, leading to a single nanoparticle encapsulation with a core‐shell structure. As expected, the dense interfacial layer on the peptide nanoparticle surface achieves a superior loading degree of up to 95.4%. What's more, once the core‐shell structure is established, the peptide mass fraction in individual encapsulation always exceeds 90% even under fierce external force. Following the individual nanoparticle encapsulation, the insulin‐polycation complex (InsNp@PEI) reduces the inflammation from polymer and displays an effective glycemic control in type 1 diabetes. Overall, the newly developed single surface decoration encapsulates peptides with ultrahigh efficiency and opens up the possibility for further encapsulation.