The role of intermolecular interactions on the encapsulation of human insulin into the chitosan and cholesterol-grafted chitosan polymers

Abstract

Chitosan and its derivatives used in drug delivery investigations could contribute to improving peptide and protein drug delivery systems. Herein, the molecular dynamics (MD) simulation approach was applied to evaluate the important driving factors of the human insulin encapsulation into the chitosan and cholesterol-modified chitosan polymers. The MD results revealed that the native conformation of insulin was stabilized by the chitosan polymers. In the present study, the effect of cholesterol moieties of modified chitosan was also examined and the results indicated that the cholesterol components would decrease the tendency of chitosan polymers to human insulin. Further analyses showed that the intermolecular interactions between the tyrosine, phenylalanine, and acidic residues are important in the formation of the insulin-polymer complexes. Another interesting finding was that the van der Waals, electrostatic, and CH-π interactions play key roles in the encapsulation process. Generally, in the case of human insulin, the MD simulation results would seem to suggest that the chitosan nanoparticles could be the more suitable carrier than the cholesterol-grafted chitosan nanoparticles.

Keywords: Binding free energy; Chitosan; Cholesterol-modified chitosan; Human insulin; Molecular dynamics simulation; Protein drug delivery.