Intranasal delivery of insulin: An update on status quo and challenges for diabetes treatment

Diabetes mellitus is a chronic metabolic disorder characterised by either autoimmune-mediated destruction of pancreatic β-cells or impaired physiological responses to circulating insulin. Conventional subcutaneous insulin administration does not achieve optimal pharmacokinetics due to delayed systemic absorption and its inability to replicate the prandial, pulsatile secretion pattern of endogenous insulin. In contrast, intranasal insulin delivery offers a promising non-invasive alternative, with a pharmacokinetic profile that more closely mirrors physiological insulin release following meals, thereby improving postprandial glycaemic control. This review outlines the advantages and limitations of the intranasal route for insulin administration in comparison to other delivery methods. It also describes the structural and physiological barriers of the nasal cavity, and the specific challenges associated with delivering protein therapeutics via this route. Emphasis is placed on strategies designed to enhance the mucosal permeation of insulin, including the use of nanotechnology, safe absorption enhancers and mucoadhesive polymers, drug complexation, and the development of particulate and responsive drug delivery systems. Finally, recent advances in clinical and preclinical studies of intranasal insulin formulations are discussed, highlighting the translational potential of this approach in diabetes management.