A Novel Oral Protein-Drug Delivery System with Bilayer Shell-Core Structure

Abstract

For oral drug therapy, the inefficiency of protein/peptide drugs is a big concern due to inactivation and degradation induced by the gastric juice. In this study, a novel highly effective drug delivery system with the bilayer shell-core structure was developed for oral administration of protein/peptide drugs. In this design, chitosan microparticle was used as the carrier core to load protein drug via genipin crosslinking, and then covered by a casein protective shell via TG crosslinking to slow release the loaded drug and protect its bioactivity. In order to verify the effectiveness of this drug delivery system, the novel thrombolytic agent, nattokinase, was loaded and applied to prevent thrombosis via oral administration in mice. The results indicated that the bilayer shell-core structure could protect loaded nattokinase from destroy in the gastric juice, and then release both intact nattokinase and digested fragments with thrombolytic activity gradually in the intestine. Results from mouse black tail test indicated that oral administration of this microparticle could preclude thrombus formation in the tail. Overall, this study provides a feasible way to enhance the oral bioavailability and prolong the effective half-life of protein drugs, which has the potential to accelerate the development of oral drug therapy.