Breaking biological barriers: Organic nanocarriers for multiroute transmucosal insulin delivery

The clinical use of therapeutic peptides such as insulin remains constrained by inefficient delivery routes that fail to achieve sufficient drug levels at target tissues. Moreover, the lifelong reliance on injectable formulations imposes considerable physical discomfort and psychological burden on patients. In response, a wide range of innovative strategies have emerged to provide less invasive, more patient-friendly, and highly bioavailable alternatives. Among these, transmucosal insulin delivery has gained particular attention due to the rich vascularization of mucosal surfaces, which enables rapid systemic absorption while avoiding the limitations of parenteral administration. Recent advances in nanoscience and nanotechnology have accelerated the development of novel delivery systems capable of protecting insulin from hostile physiological environments and enhancing its transport across mucosal barriers. In this review, we summarize the progress of organic nanosystems, specifically lipid-based and polymer-based nanocarriers, as promising platforms for noninvasive insulin administration via nasal, ocular, buccal, sublingual, and inhalation routes.