Delivery of liothyronine by microneedle patch for the treatment of hypothyroidism

Hypothyroidism is conventionally treated with thyroid hormone replacement via synthetic hormones, namely levothyroxine (LT₄), and in possible combination with liothyronine (LT₃), both administered orally. The supratherapeutic peaks and subtherapeutic troughs of LT₃ concentration after oral delivery may limit efficacy, as this pharmacokinetic profile does not mimic the relatively constant T₃ levels found in normal physiology. Microneedle patches (MNPs) provide a simple-to-use delivery method that can be formulated to achieve controlled drug release for extended periods of time. Here, we developed a MNP for LT₃ delivery into the skin as a first assessment of this approach. After examining a number of MNP formulations, we developed MNPs containing a range of different LT₃ doses in a poly(vinylpyrrolidone)-based formulation. The MNs effectively punctured the skin and achieved average LT₃ delivery efficiencies of 41-71%. LT₃ MNP administration to hypothyroid rats at three doses (10 µg, 100 µg, 1000 µg) produced elevated serum T₃ levels that persisted for 18-24 h, exhibiting a nonlinear dependence on LT₃ dose. This study established the feasibility of administering LT₃ by MNP that could be translated to enable improved therapy for patients with hypothyroidism.