Preparation and characterization of CS/γ-PGA/PC complex nanoparticles for insulin oral delivery

In recent years, natural polyelectrolyte complex chitosan/poly-γ-glutamic acid (CS/γ-PGA) has emerged as a promising nanocarrier delivery system for drug delivery due to its non-toxic and easily degradable properties. However, tightly bound CS/γ-PGA complexes often lead to lower encapsulation efficiency of peptide drugs without coordination of metal ions. In this investigation, we find that procyanidin (PC), as a cross-linking agent, is able to combine with CS and insulin through hydrogen bonding, which significantly improve encapsulation efficiency of insulin up to 90% in CS/γ-PGA/PC complex nanoparticles (CNPs). The results of this study demonstrate that CNPs release insulin in a pH-dependent approach and greatly reduce its enzymatic degradation in vitro. The transepithelial permeability of the CNPs is 8.1-fold higher than that of native insulin via both endocytosis and paracellular passways. Further pharmacokinetic studies reveal an oral pharmacological availability of 9.81 ± 1.32% in type I diabetic rats after intragastric administration of freeze-dried CNPs which loaded in enteric-coated capsules. In consequence, CNPs not only improve oral bioavailability of insulin but also are a promising delivery platform for insulin or other peptide/protein drugs.