Fabrication of gelatin methacryloyl hydrogel microneedles for transdermal delivery of metformin in diabetic rats

Injection therapy for diabetes has poor patient compliance, and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients. In this work, to demonstrate the benefits of an alternative drug delivery technique that overcomes these issues, methacrylated gelatin hydrogel-forming microneedles integrated with metformin were developed to adjust blood glucose levels in diabetic rats. Gelatin methacryloyl microneedles (GelMA-MNs) with different degrees of substitution were successfully prepared by a micro-molding method. The resultant GelMA-MNs exhibited excellent mechanical properties and moisture resistance. Metformin, an anti-diabetic drug, was further encapsulated into the GelMA-MNs, and its release rate could be controlled by the three-dimensional cross-linked network of microneedles, thereby exhibiting sustained drug release behaviors in vitro and implying a better therapeutic effect compared with that of subcutaneous injection in diabetic rats. The drug release period could be significantly prolonged by improving the cross-link density of GelMA-MNs. The results of hypoglycemic effect evaluation show that the application of GelMA-MNs for transdermal delivery in diabetic rats has promising benefits for diabetes treatment. Graphic abstract