Cp1-11 peptide/insulin complex loaded pH-responsive nanoparticles with enhanced oral bioactivity

To improve the oral efficiency of insulin, a novel oral insulin delivery system was developed, to protect the insulin from destruction, and to deliver monomeric insulin with higher bioactivity. The oral insulin delivery system was developed by using chitosan/alginate nanoparticles as carriers for the oral delivery of Cp1-11 peptide/insulin complex (Cp1-11 peptide/Insulin Loaded Nanoparticle, CILN). There is a supramolecular interaction between the insulin and the Cp1-11 peptide, which could inhibit insulin aggregation and improve its bioactivity. In vitro release studies showed that the pH-responsive CILN system could retain insulin in a simulated gastric buffer solution, and exhibited sustained release of the insulin in simulated intestinal buffer solution. The stability studies indicated that CILN could also protect insulin against degradation by proteases in the gastrointestinal tract. Moreover, the insulin oral delivery system appeared to show excellent hypoglycemic effect, and led to higher pharmacological availability of insulin, compared with free insulin loaded nanoparticles, in diabetic rats. Thus, this study has suggested that insulin complexed with Cp1-11 peptide, followed by encapsulating in chitosan/alginate nanoparticles, providing an effective strategy for an oral insulin delivery system to treat diabetes in the future.