Arginine end-functionalized poly( l-lysine) dendrigrafts for the stabilization and controlled release of insulin

Arginine end-functionalized biodegradable poly( l-lysine) dendrigrafts exhibit high levels of insulin complexation efficiency and effectively protect complexed insulin against enzymatic degradation. Insulin release rates are controlled by the number of arginine end-groups. [Display omitted] ► Arginine functionalized poly( l-lysine) dendrigrafts interact with insulin. ► High levels of insulin complexation efficiency are registered. ► Complexed insulin is effectively protected against enzymatic degradation. ► Insulin release rates are controlled by the number of arginine end-groups. Second generation biodegradable poly( l-lysine) dendrigrafts functionalized with 12–48 arginine end-groups interact, at physiological pH, with insulin affording dendrigraft/insulin complexes as established by dynamic light scattering, ζ-potential, circular dichroism and isothermal titration calorimetry. Binding occurs in two steps; at low dendrigraft/insulin molar ratios (⩽0.07) interaction is accompanied with the endothermic dissociation of insulin dimers, while at higher molar ratios, complexation of insulin monomers with dendrigraft derivatives occurs exothermically. High levels of insulin complexation efficiencies (>99%) were determined for all derivatives. Stabilization of complexed insulin against enzymatic degradation by trypsin and α-chymotrypsin is observed especially for the highly arginine end-functionalized dendrigrafts. Insulin release rates in simulated intestinal fluid are being controlled by the number of arginine end-groups and released insulin retains its conformation.