Why Most Oral Insulin Formulations do Not Reach Clinical Trials

Abstract

Oral insulin able to induce an efficient antihyperglycemic effect either to replace or complement diabetes mellitus therapy is the major goal of health providers, governments and diabetic patients. Oral therapy is associated not only with the desire to exclude needles from the daily routine of diabetic patient but also with the physiological provision of insulin they would get. Despite numerous efforts over the past few decades to develop insulin delivery systems, there is still no commercially available oral insulin. The reasons why the formulations developed to administer insulin orally fail to reach clinical trials are critically discussed in this review. The principal features of nanoformulations used so far are also addressed as well as the undergoing clinical trials.

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

“…5 However, oral delivery of insulin has two main bottlenecks, the harsh and degrading enzymatic situation of the gastrointestinal tract that inactivates insulin very quickly and the mucosal barrier that limits insulin's oral bioavailability. 6,7 Numerous approaches have been applied to bypass the enzyme barrier, and some of them have achieved promising results.…”

Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials

“…In spite of this, insulin remains one of the main candidates for oral delivery [1,4], but it is a particularly problematic molecule due to risks of hypoglycaemia due high interand intra-subject variability in oral bioavailability, sensitivity to intestinal proteases, and low permeation across the small intestinal epithelium (Fig. 1).…”

New Insulins, Biosimilars, and Insulin Therapy

“…For a long time, the quest for oral insulin administration has been explored, but with little success (6)(7)(8). Subcutaneously administered insulin is taken up by the peripheral circulation, whereas oral insulin can more closely mimic normal physiology by being absorbed from the gastrointestinal tract and via the portal vein be delivered directly to the liver.…”