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.