Advances in Nanomedicine-Enabled Transdermal Patches for Insulin Delivery: From Design to Clinical Translation

Insulin injection remains the best therapy for diabetes mellitus, but subcutaneous injection continues to pose challenges, including patient discomfort, poor compliance and fluctuating plasma glucose profiles. Recently, transdermal insulin delivery has emerged as a non-invasive strategy that bypasses gastrointestinal degradation and first-pass hepatic metabolism, thereby increasing insulin bioavailability and enhancing patient acceptance. Recent developments in nanomedicine have facilitated the development of transdermal patches with enhanced drug encapsulation, uptake and controlled release. Nanostructured lipid carriers, polymeric nanocomposites, liposomes and SLNs have demonstrated a five-fold enhancement of transdermal flux and an extended insulin effect in preclinical models. The addition of ionic liquids and polymeric nanogels leads to an additional increase in insulin aqueous solubility and permeation, resulting from the temporary regulation of stratum corneum lipid organization. Bright and stimuli-responsive patches with glucose oxidase or phenylboronic acid functional groups enable regulated insulin delivery in response to changes in blood glucose, demonstrating near-normoglycemia for up to 48 h in animal testing. Nanocomposite systems assisted by microneedles have also been advanced to the early clinical phase, offering enhanced reproducibility of their pharmacokinetics and a low risk of dermal irritation. Despite these encouraging results, several translational challenges remain, such as biocompatibility, repeatability in the production of nanocarriers, long-term stability of formulations and regulatory standardization. This review examines the physicochemical design principles, materials innovations and permeation mechanism of nanomedicine-engineered insulin patches, the current state of preclinical and clinical advancements, challenges in production and future perspectives in viable patient-focused transdermal insulin delivery.