Transdermal Insulin Application System with Dissolving Microneedles

Background: The aim of this report was to develop a dissolving microneedle (DM) application system, where 225-300 insulin-loaded DMs were formed on a chip. After the heat-sealed sheet is removed, the system covered with the press-through package layer is put on the skin. By pressing with the hand, insulin DMs were inserted into the skin. Materials and Methods: Factors affecting the penetration depth of DM were studied using applicator in vitro and in vivo experiments. The penetration depth was determined for rat and human skin. Two-layered DM array chips were prepared to obtain complete absorption of insulin and administered to the rat abdominal skin. Plasma glucose levels were measured for 6 h. By comparing the hypoglycemic effect with that obtained after subcutaneous injection, relative pharmacological availability (RPA) was determined. Results: The penetration depth increased from 21 +/- 3 mu m to 63 +/- 2 mu m in proportion to application speed to isolated rat skin, at 0.8-2.2 m/s. Human skin showed similar results in the penetration depth. The in vivo penetration depth was dependent on the force (0.5-2.5 N) and duration (1-10 min), as the secondary application force. The penetration depth was 211 +/- 3 mu m with a duration of 3 min in the in vivo rat experiment. DM array chips having an insulin-loaded space of 181.2 +/- 4.2 and 209 +/- 3.9 mu m were evaluated in the rat. RPA values of insulin from DMs were 98.1 +/- 0.8% and 98.1 +/- 3.1%, respectively. Conclusions: These results suggest the usefulness of the two-layered DM application system for the transdermal delivery of insulin.