Mussel-inspired biphasic microneedle patch for long-acting hypothyroidism treatment

Hypothyroidism, caused by insufficient thyroid hormone production or impaired responsiveness, is typically managed with lifelong daily oral levothyroxine sodium (LT₄). However, oral administration often suffers from variable gastrointestinal absorption and poor adherence. Here, we report a mussel-inspired biphasic microneedle (MN) patch integrating LT₄ microcrystals and a bioadhesive PDA-PAM hydrogel backing for sustained and patient-friendly hypothyroidism management. The biphasic MNs, composed of rapidly dissolving PVA/sucrose tips and a robust polystyrene base, efficiently deposit LT₄ microcrystals intradermally upon insertion, enabling gradual dissolution and sustained release. The hydrogel backing offered strong and flexible adhesion, ensuring reliable skin attachment during movement. In vitro, the patches exhibited first-order LT₄ release for 9 days. In hypothyroid rats, a single patch application maintained therapeutic plasma LT₄ concentrations for ∼6 days, with bioavailability comparable to intravenous injection. In a preliminary study in healthy volunteers (n= 13), placebo MN patches demonstrated high insertion efficiency, good short-term tolerability, and favorable user acceptability. While further studies are required to establish long-term safety and efficacy in patients with hypothyroidism, these findings support the feasibility of a minimally invasive, extended-interval LT₄ delivery strategy.