Bioinspired Long-Acting Mucoadhesive Gastric Patch for Levothyroxine Delivery.

The delivery of long-acting therapeutic dosage forms through the oral route is a challenge. A bioinspired mucoadhesive gastric patch was developed as a platform technology for the long-acting delivery of levothyroxine sodium (LT). The mucoadhesive patch was designed to have a three-layer composition, including a core, mucoadhesive, and backing layer. The water contact angle on the mucoadhesive and backing layer sides of the patch was found to be 68 ± 1.4° and 121 ± 0.4°, respectively. The adhesive strength of the mucoadhesive layer, made of a 4-carboxyphenylboronic acid-chitosan conjugate, was found to be 25 ± 1.1 kPa when adhered to the rat stomach mucosa. The LT-containing patch was found to remain adhered to the body region of the rat stomach after 30 days of oral administration. A single dose of the mucoadhesive gastric patch containing 15.8 μg/kg/day of LT was able to provide a constant plasma concentration (87-126 ng/mL) of LT for 38 days in rats. There was no significant (P < 0.05) difference in the concentration of inflammatory markers including tumor necrosis factor-α (TNF-α), interleukins 1β (IL-1 β) and 6 (IL-6), with and without long-acting patch administration. The patches were found to be stable when stored at 5 ± 3 °C for 6 months. Taken together, the bioinspired mucoadhesive gastric patch can be developed for the long-acting delivery of LT through the oral route.