Abstract
Parenteral administration of insulin remains the most common route of administration, causing local hypertrophy at the injection sites because of multiple daily injections. Because of this, there is an interest and effort in oral insulin administration that is convenient and mimics the physiology of endogenous insulin secreted in the liver. However, oral insulin encountered different challenges due to abundant enzyme degradation, the presence of a mucus layer, and the underlying intestinal epithelial membrane barrier in the gastrointestinal tract. This narrative review reviewed the literature dealing with novel oral insulin delivery approaches. Various pieces of literature were searched, filtered, and reviewed from different sources, and the information obtained was organized, formulated, and finalized. Oral insulin has been formulated and extensively studied in various novel delivery approaches, such as nanoparticles, microspheres, mucoadhesive patches, encapsulations, hydrogels, ionic liquids, liposomes, and complexation. The efficiency of these formulations demonstrated improved efficiency and potency compared to free oral insulin delivery, but none of them have greater or equivalent potency to subcutaneous insulin. Future studies regarding dose-dependent therapeutic efficacy and the development of new novel formulations to produce comparable oral insulin to subcutaneous insulin are warranted to further support the suitability of the current platform for oral insulin delivery.