3D printed mucoadhesive gastric patch provides long-acting naltrexone delivery.

The aim of the study was to fabricate, characterize and evaluate 3D printed mucoadhesive gastric patch that can provide long-acting drug delivery. Naltrexone - an opioid antagonist approved to treat opioid and alcohol dependence disorder - was used as the model hydrophilic drug. The core layer of mucoadhesive patch was 3D printed using printing ink made of polycaprolactone, polylactic acid, sodium carboxymethylcellulose, Eudragit RS 100, Carbopol 934P, and polyethylene glycol 400. The 3D printed core layer was coated with mucoadhesive layer (composed of chitosan-carboxyphenyl boronic acid conjugate) on one side and backing layer (composed of polycaprolactone and polydimethylsiloxane) on the other side. The 3D printed patch was characterized for tensile strength, surface morphology, swelling index, contact angle. The in vitro release study showed 100 % NTX release from mucoadhesive patch in 98 days. The ex vivo gastric mucosal permeation studies showed 177 ± 17 and 872 ± 68 µg/cm2 of NTX permeated through the mucosal side of rat stomach from NTX patch and solution, respectively. The pharmacokinetic studies in rat model showed that a single oral administration of NTX patch was able to sustain the plasma concentration of NTX for 35 days equivalent to the daily administration NTX solution. The plasma levels of the inflammatory markers such as interleukin-1β, interleukin-6, and tumor necrosis factor-α were comparable to the baseline values. In conclusion, 3D printed mucoadhesive gastric patch can be developed for long-active delivery of NTX.