A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery

Pharmaceutical scientists have long struggled to develop reliable and efficient systems of administering insulin orally due to multiple barriers, including stomach acidity, enzymatic degradation, and mucus barriers. However, various strategies were developed to avoid insulin degradation in the gastrointestinal tract (GIT) and promote membrane permeability and biological activity. Among these strategies, chitosan polymer-based carriers are widely researched due to their ability to protect insulin in the alimentary canal and deliver it effectively through the intestinal mucosa, improving its bioavailability. To improve chitosan properties, chemical and physical modifications have been developed, and recently, nanoparticles, microparticles, and beads of chitosan exhibited potential systems for oral insulin delivery (OID). This review facilitates an outline of the types of diabetes mellitus, insulin biosynthesis, and gastrointestinal barriers against oral insulin. Moreover, the limitations of subcutaneous insulin delivery and alternative routes of administration are also discussed. As an ideal and most convenient oral administration route, the challenges of safe insulin delivery through the GIT and strategies to elevate its bioavailability are highlighted. In addition, this review focuses on recent advancements in chitosan based carriers for OID and their potential future applications. Graphical Abstract