Novel non-invasive methods of insulin delivery

Insulin has usually been administered subcutaneously in the treatment of diabetes mellitus. Alternative delivery routes of insulin are expected to overcome some limitations, mainly concerned with the possibility of hypoglycemia episodes, weight gain and inadequate post-meal glucose control, in order to lead a better patient compliance.

This review article covers all the most relevant non-invasive insulin delivery methods under development, respective technology and clinical data available according to their status of development. Special focus is given to the systems with late clinical trial evidences, their achievements and pitfalls. Pulmonary and oral appear to be the most advantageous routes, with regard to the long list of potentially marketed products.

Alternative insulin delivery to the subcutaneous administration is more and more close to the success, being fundamental that any optimized technology could overcome the overall low mucosal bioavailability of insulin, mostly due to its early degradation before absorption, inactivation and digestion by proteolytic enzymes and poor permeability across mucosal epithelium because of its high molecular weight and lack of lipophilicity.