Surface Decoration of Peptide Nanoparticles Enables Efficient Therapy toward Osteoporosis and Diabetes

Abstract A versatile surface decoration strategy to efficiently encapsulate water‐soluble peptides is developed. By assembling peptide molecules into nanoparticles, diverse physiochemical properties of these compacted molecules are equalized to the surface properties of nanoparticles. Primarily driven by the generic electrostatic attractions, the surface of as‐prepared peptide nanoparticles is decorated with charged amino acids‐grafted poly(lactic‐co‐glycolic acid). This adsorbed polymer layer versatilely blocks the phase transfer of peptide nanoparticles by increasing their affinity to the dispersed phase solvent molecules. Attributed to the ultrahigh encapsulation efficiencies (> 96%), the peptide mass fraction inside the obtained microcomposites is higher than 48%. The plasma calcium level has been efficiently reduced for ≈3 weeks with only one single injection of salmon calcitonin‐encapsulated microcomposite in osteoporotic rats. Similarly, one single injection of exenatide‐encapsulated microcomposites efficiently controls the glycemic level in type 2 diabetic rats for up to 3 weeks. Overall, the developed versatile surface decoration strategy efficiently encapsulates peptides and improves their pharmacokinetic features, regardless of the molecular structure of peptide cargos.