Design of virus-mimicking polyelectrolyte complexes for enhanced oral insulin delivery.

Abstract

The viscous and elastic mucus layer is still an undesirable barrier for oral insulin delivery. To solve the problem, virus-mimicking nano-sized polyelectrolyte complex (PEC) was designed and their capacity in enhancing peroral insulin absorption in combination with bifunctional material SDS coating was investigated. Inspired by nature, virus-mimicking chitosan (CS)-modified L-Phe derivatives were synthesized to simulate the components of viral envelopes and then PECs between CS-g-N-Phe copolymers and insulin were prepared to achieve both structure and composition simulation of virus envelop. Based on the results from both in vitro and in vivo studies, it was concluded that in vitro mucodiffusion and in vivo hypoglycemic effect were dependent on L-Phe graft ratio, with CS-g-N-Phe20.2%/Insulin PECs presenting 2.0-2.2 fold higher relative pharmacological bioavailability than non-modified CS/Insulin PECs. Thereafter, SDS solution was applied as outer layer coating on the surface of virus-mimicking PECs. The coated PECs showed improved enzymatic stability, enhanced transport across mucus layer as well as intestinal epithelium in a SDS concentration dependent manner, with 0.6% SDS coating presenting the best effect, with further enhanced relative pharmacological bioavailability in healthy rats and prolonged therapeutic effect up to 9h.