Cell penetrating and transytosing peptides: powerful strategies for oral insulin delivery

 Insulin is essential for type 1 and advanced type 2 diabetes to maintain blood glucose levels and increase the patient’s longevity. Frequent subcutaneous insulin injections are usually associated with pain, local tissue necrosis, infection and nerve damage. Recently, a number of new delivery methods such as oral insulin delivery have been developed to overcome these limitations and increase patient’s satisfaction. Oral delivery of insulin and other therapeutic peptides/ proteins are associated with poor intestinal absorption and enzymatic degradation in the gastrointestinal tract. However, Cell Penetrating (CPPs) and transytosing peptides have exhibited promising potential as carriers that conjugated to insulin and capable to across the intestinal epithelium. Numerous studies have shown that after conjugation of insulin with CPPs and transytosis peptides these biomolecules can retain their biological activity and also are stable and resistant to proteolytic degradation. In this review, following the introduction of different types of CPPs and also transytosis peptides, we have focused on the studies that they use these peptides as a powerful technology for oral insulin delivery. Based on the results of these studies, oral insulin will not only be a good candidate for painful injections in diabetic patients, but also mimics the physiology of endogenous insulin secreted by pancreas.