Fabrication and mechanical/biological evaluations of dissolving bird-bill microneedle arrays

Coated microneedles (MNs) have several disadvantages, including limited drug doses, decreased skin puncture ability due to drug coating, and a risk of clogging and infection due to repeated application. We aimed to fabricate a dissolving bird-bill MN (dBB MN) with a vertical groove between two thin plate-shaped needles and needle pedestal. Moreover, we evaluated its ability to transdermally deliver a large-molecular-weight insulin into the systemic circulation. Hydrogels with various concentrations of polyvinylpyrrolidone (PVP) or sodium hyaluronate (HA) were prepared, and dBB MN arrays were fabricated by micromolding under negative pressure for potential mass production. The needle height of the dBB MN was at the maximum when the hydrogel was 25 w/w% PVP, with a viscosity of 8-9 Pa∙s. Furthermore, the buckling force of dBB MNs made from 25 w/w% PVP was 130.6 ± 51.0 mN, which increased to 195.6 ± 65.3 mN when insulin was added at 1 w/w%. The skin insertion ability of dBB MN was investigated using swain skin, with micro-holes were confirmed on the skin surface. dBB MN showed biphasic dissolution in the skin; the plate-shaped needles were immediately dissolved within 10 min, while the needle pedestal was slowly dissolved over 180 min. The blood glucose concentration in diabetic rats decreased slowly and significantly after a 3-h application of the insulin-loaded dBB MN array. Therefore, the dBB MN array demonstrated sufficient ability to puncture skin and transdermally deliver a large-molecular-weight drug into the systemic circulation. These findings suggest that the dBB MN array holds promise as a minimal invasive drug delivery platform, with potential applications in improving patient adherence and expanding access to essential therapies, particularly in resource-limited settings.