Abstract: Microneedle technology has emerged as a potential new means of painless drug delivery for diabetic patients. Maintaining blood glucose levels (BGLs) within the normal range for a long time is important for people with diabetes. However, it is a new challenge to realize long-term therapy due to insufficient drug loading. In this study, a polymeric porous microneedle array with continuous micropores was prepared by combining the microtemplate method and pore-causing agent method. By changing the ratio of a pore-causing agent, the fluid uptake capacity and mechanical strength were adjusted to balance the trade-off between rapid imbibition and the mechanical properties of puncture. A special drug loading chamber was developed to realize a large package (135.69 mg) of metformin-loaded porous microneedle system. Experiments in diabetic rat models in vivo showed that the prepared porous microneedles can effectively puncture the skin and maintain stable BGLs up to 7 h ×5 cycles over five experimental cycles (108 h) without the risk of hypoglycemia. These results suggested that the high-dose polymeric porous microneedle-mediated metformin delivery system had the advantages of rapid response and durable release, and was a potential candidate for sustained-release transdermal drug delivery in patients with diabetes mellitus and even chronic conditions.

Keywords: porous microneedles; transdermal drug delivery; blood glucose levels; diabetes