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.