Surface Adsorption‐Mediated Ultrahigh Efficient Peptide Encapsulation with a Precise Ratiometric Control for Type 1 and 2 Diabetic Therapy

Abstract A surface adsorption strategy is developed to enable the engineering of microcomposites featured with ultrahigh loading capacity and precise ratiometric control of co‐encapsulated peptides. In this strategy, peptide molecules (insulin, exenatide, and bivalirudin) are formulated into nanoparticles and their surface is decorated with carrier polymers. This polymer layer blocks the phase transfer of peptide nanoparticles from oil to water and, consequently, realizes ultrahigh peptide loading degree (up to 78.9%). After surface decoration, all three nanoparticles are expected to exhibit the properties of adsorbed polymer materials, which enables the co‐encapsulation of insulin, exenatide, and bivalirudin with a precise ratiometric control. After solidification of this adsorbed polymer layer, the release of peptides is synchronously prolonged. With the help of encapsulation, insulin achieves 8 days of glycemic control in type 1 diabetic rats with one single injection. The co‐delivery of insulin and exenatide (1:1) efficiently controls the glycemic level in type 2 diabetic rats for 8 days. Weekly administration of insulin and exenatide co‐encapsulated microcomposite effectively reduces the weight gain and glycosylated hemoglobin level in type 2 diabetic rats. The surface adsorption strategy sets a new paradigm to improve the pharmacokinetic and pharmacological performance of peptides, especially for the combination of peptides.