Oral insulin delivery for treatment of diabetes mellitus

Abstract

Diabetes mellitus is characterized by a condition known as hyperglycemia which may be controlled through medication and insulin. Current insulin therapy for diabetes mellitus involves frequent dosing of subcutaneous injections, causing local discomfort, patient incompliance, hypoglycemia, and hyperinsulinemia, among others, one of the approaches to overcoming these issues is to administer insulin through oral route. An oral form of insulin has been the elusive goal for many investigators since the protein initial discovery by Banting and Best in 1922. Oral delivery of insulin is one of the promising and anticipated areas in the treatment of diabetes, primarily because it may significantly improve the quality of life of patients who receives insulin regularly. However, there are several challenges in developing an oral route for insulin delivery; include low bioavailability due to rapid enzyme degradation in the stomach, inactivation, and digestion by proteolytic enzymes in the intestinal lumen, poor permeability, and poor stability. Several companies have developed technology platforms that protect polypeptides and proteins from enzymatic hydrolysis, enable their transport across the epithelial lining, and promote their absorption from the GI tract. Most notably, the use of permeation enhancers, protease inhibitors, enteric coatings, and polymer microsphere formulation will be covered, including commentary on which methods hold more promise towards the successful development of oral insulin. This review, considers the current literature on the advances, methods, needs, and challenges in the development of oral insulin.