Nanocarrier-based insulin delivery: A leap towards a needle-free future

The burden of diabetes mellitus continues to escalate globally, demanding innovative and patient-centric therapeutic alternatives to conventional insulin injections. Nanocarrier-based drug delivery systems offer transformative potential in diabetes management by enabling needle-free, targeted, and sustained insulin administration. This review not only explores the cutting-edge landscape of nanocarriers—liposomes, polymeric nanoparticles, dendrimers, micelles, and nanoemulsions—but also uniquely integrates clinical trial outcomes, molecular mechanisms, and novel applications such as CRISPR-based gene therapy and dietary extracellular vesicles (ELVs). These platforms shield insulin from enzymatic breakdown, enable oral or transdermal delivery, and provide controlled release to simulate physiological insulin profiles. Future uses encompass gene-loaded nanocarriers for regenerating pancreatic beta cells and intelligent nanocarriers integrated with biosensors for real-time glucose-responsive insulin release. This union opens the way for self-directed diabetes management with minimal patient interaction. Albeit promising, problems like potential toxicity, financial impediments, and regulatory issues have to be solved through collaborative efforts involving interdisciplinary inputs. Notably, the coupling of nanocarrier technology with wearable technology and personalized medicine techniques signals a shift in diabetes care paradigms. With maturity in research, these smart systems might not only obviate the need for syringe dependence but also redefine treatment by merging bioengineering, diagnostics, and regenerative strategies. Nanomedicine's role is poised to shift diabetes care from symptom management to functional cure, with global implications for improving patient quality of life. • Nanocarriers enable targeted and sustained insulin delivery, reducing injection dependency. • Oral insulin via nanocarriers improves bioavailability and enhances patient compliance. • Smart nanocarriers integrate with wearables for real-time, automated diabetes management. • Gene therapy with nanocarriers offers hope for regenerating pancreatic beta cells. • Despite promise, challenges in safety, cost, and regulation must be addressed for clinical use.