A universal powder-laden crosslinked chitosan microneedle patch for high-dose controllable drug delivery.

In this study, we constructed a novel powder-laden core-shell crosslinked chitosan microneedle patch for high-dose and controllable delivery of various drugs, including both macromolecular biological drugs and small-molecule chemical drugs. Direct loading of drug powders greatly improved drug loading capacity and minimized degradation. The results of the in vitro drug release study suggested that the release behaviors of the most tested drugs (both macromolecular drugs and small-molecule drugs) can be tuned by adjusting the crosslink density of the microneedle shell to achieve either rapid or sustained release of the loaded drug. The in vivo hypoglycemic efficacy test in streptozotocin-induced diabetic mice further proved that the onset and duration of the insulin-laden patch can be customized by adjusting the crosslink density. Furthermore, a combination of microneedle patches with different crosslink densities not only rapidly reduced blood glucose levels to normoglycemic levels (within 1 h) but also maintained normoglycemia for up to 36 h. The insulin loaded in the patch also showed good stability during storage at 40 °C for 6 months. Our results suggest that this powder-laden patch represents a strong candidate for addressing the multiple challenges in the preparation and application of polymeric microneedles and shows promise in clinical applications.