A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin

• Glucose-responsive nanocarriers for loading of insulin were prepared.
• Insulin-loaded glucose-responsive nanocarriers were further encapsulated into a HA hydrogel.
• The composite hydrogel system provide a multi-protection for insulin during oral delivery process.
• The hypoglycemic effect for oral delivery of insulin was studied in vivo.
• The findings provide a new way in diabetes treatment via oral ingestion.

Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers.

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