Janus LAAM-loaded electrospun fibrous buccal films for treating opioid use disorder.

Abstract

The opioid crisis has claimed approximately one million lives in the United States since 1999, underscoring a significant public health concern. This surge in opioid use disorder (OUD) fatalities necessitates improved therapeutic options. Current OUD therapies often require daily clinical visits, leading to poor patient compliance and high costs to the health systems. Levo-alpha-acetylmethadol (LAAM) is a long-lasting OUD drug, and the thrice-weekly oral LAAM solution can offer better patient compliance compared to the traditional daily methadone therapies. However, LAAM is FDA-approved but withdrawn from the market. As part of the NIH HEAL Initiative, we aim to reintroduce LAAM back to the market to improve OUD therapeutic options by developing a novel Janus LAAM-loaded fibrous buccal film (LFBF) formulation made of a drug-containing electrospun fibrous layer and a backing layer. The buccal administration of LFBF exhibited superior transmucosal delivery of LAAM to systemic circulation with a nearly 4-fold higher drug bioavailability than the conventional oral LAAM solution in rabbits. Furthermore, upon buccal administration in an opioid-dependent rat model, the LFBF significantly decreased fentanyl choice in the fentanyl-dependent rats, while the conventional oral LAAM solution did not at the same dose. Both the buccal film and oral solution of LAAM reduced somatic withdrawal signs in the experimental animals. These findings highlight the buccal delivery of LAAM using electrospun fibers as a promising strategy with improved drug bioavailability. Furthermore, it sheds light on future clinical applications aiming for enhanced treatment outcomes in the battle against the current opioid crisis.