Abstract

Frequent insulin injections remain the primary method for controlling the blood glucose level of individuals with diabetes mellitus but are associated with low compliance. Accordingly, oral administration has been identified as a highly desirable alternative due to its non-invasive nature. However, the harsh gastrointestinal environment and physical intestinal barriers pose significant challenges to achieving optimal pharmacological bioavailability of insulin. As a result, researchers have developed a range of materials to improve the efficiency of oral insulin delivery over the past few decades. In this review, we summarize the latest advances in material design that aim to enhance insulin protection, permeability, and glucose-responsive release. We also explore the opportunities and challenges of using these materials for oral insulin delivery.

Highlights

• Acid- and enzyme-resistant materials are designed to protect insulin from the harsh gastrointestinal environment.

• Zwitterionic materials, cell-penetrating peptides or ligands modified materials improve intestinal permeability.

• Glucose-responsive moiety achieves on-demand release of insulin and desirable diabetes management.