A bilayer microneedle for therapeutic peptide delivery towards the treatment of diabetes in db/db mice

Abstract Microneedles (MN) provide an alternative approach to hypodermic injection for the delivery of biomacromolecule in a minimally invasive manner. In this work, lixisenatide-loaded bilayer MNs were prepared using polyvinylpyrrolidone K29/32 (PVP K29/32) as the matrix material via a two-step molding method to avoid therapeutic wastes in the base layer. The MNs obtained in our study displayed good shapes and sufficient mechanical strength. After insertion into the rat skin, the needles of MNs fully dissolved in less than 3 min to release the therapeutic payloads. The Franz cell based transdermal permeation study revealed that the MNs could dramatically promote transdermal permeation efficiencies of the water-soluble rhodamine B and FITC-dextran (5 kDa). The skin insertion of MNs caused slight irritation and the skin recovered shortly. Also, the PVP K29/32-based MNs displayed minimum cytotoxicity against HaCaT cells and murine L929 cells. The in vivo pharmacodynamic study in db/db mice demonstrated that the MNs successfully delivered Lix and downregulated the blood glucose levels. Overall, the PVP K29/32-based bilayer fast-dissolving MNs offer a unique transdermal delivery system which can be further explored to a variety of biological therapeutics.