Delivery of liothyronine by microneedle patch for the treatment of hypothyroidism

Hypothyroidism is conventionally treated with thyroid hormone replacement via synthetic hormones, namely levothyroxine (LT 4 ), and in possible combination with liothyronine (LT 3 ), both administered orally. The supratherapeutic peaks and subtherapeutic troughs of LT 3 concentration after oral delivery may limit efficacy, as this pharmacokinetic profile does not mimic the relatively constant T 3 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 LT 3 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 LT 3 doses in a poly(vinylpyrrolidone)-based formulation. The MNs effectively punctured the skin and achieved average LT 3 delivery efficiencies of 41–71%. LT 3 MNP administration to hypothyroid rats at three doses (10 µg, 100 µg, 1000 µg) produced elevated serum T 3 levels that persisted for 18–24 h, exhibiting a nonlinear dependence on LT 3 dose. This study established the feasibility of administering LT 3 by MNP that could be translated to enable improved therapy for patients with hypothyroidism.