Towards oral insulin-controlled release nanomedicine: A review.

This article focuses on the development and challenges of oral insulin delivery using controlled-release nanomedicine (CRNM) as a non-invasive alternative to subcutaneous injections for diabetes mellitus management. It reviews various nanocarrier systems—including polymeric nanoparticles, lipid-based carriers, hydrogels, and inorganic nanoparticles—that protect insulin from enzymatic degradation, enhance intestinal absorption, and mimic physiological insulin release patterns. Advanced strategies such as glucose-responsive formulations, cell-penetrating peptides, and innovative devices like the self-orienting millimeter-scale applicator (SOMA) and luminal unfolding microneedle injector (LUMI) are discussed for improving bioavailability and patient compliance. Despite promising preclinical results and some clinical trials, translation to widespread clinical use remains limited due to challenges in stability, large-scale manufacturing, and cost-effectiveness. The article emphasizes that overcoming biological barriers and combining nanomedicine with targeted delivery pathways are critical for achieving affordable and accessible oral insulin therapies.