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.

Plugging the Leak of Nanoparticles by Interfacial Polymer Adsorption Enables an Efficient Protein and Peptide Encapsulation

“…The NP‐PLGS interaction was entropy‐driven, in which the favorable entropy increase (Δ S > 0) triumphs over the enthalpy increase (Δ H > 0). [ 15 ] This result is different from the interaction between insulin NPs and dextran derivatives (specifically, spermine‐conjugated acetalated dextran, ADS) [ 10c,14 ] which was found to be dominantly enthalpy‐driven and resulted in a loss of entropy. This discrepancy likely originates from distinct structural and attribute variations between PLGS and ADS.…”

“…[ 10c ] This approach enhances the solvation of cargo NPs and successfully inhibits the phase transfer of proteins and peptides, achieving an outstanding drug mass fraction of 77 wt.%. [ 10c,14 ]…”

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

“…As illustrated by the piezoelectric effect, the change of the oscillation frequency (Δ F 3 ) reflects the mass of polymer and solvent molecules that adsorbed on the surface of nanoparticles. 20 An ADS (20.0 mg mL −1 ) ethyl acetate solution flowed over the INS coated quartz disc for 20 min and then rinsed with ethyl acetate (Fig. 1b).…”