Novel liquid-based approaches for transmucosal drug delivery

Advancements in drug discovery, such as artificial intelligence, computational technology, and combinatorial chemistry, have led to numerous new promising drug candidates. However, most still fail to reach the market due to poor physicochemical properties, resulting in off-target or toxic effects. As a potential solution, non-invasive and targeted drug delivery at mucosal surfaces can deliver drugs directly to therapeutic sites to avoid off-target effects, decrease required drug doses, bypass hepatic first-pass metabolism, and circumvent uncontrolled drug release. Liquid-based drug delivery systems have advanced tremendously over recent years, with novel dosage forms such as ionic liquids, liquid crystals, stimuli-responsive phase transforming liquid systems, nanoemulsions, double-emulsions, self-emulsifying delivery systems, and eutectic systems being developed. These systems hold vast promise for transmucosal drug delivery as liquids generally provide superior spreadability compared to solid dosage forms, and some liquid systems provide prolonged mucosal retention times compared to conventional solutions. However, liquid dosage forms present regulatory challenges such as preservation, sterility, and stability requirements. This review discusses novel liquid-based formulation approaches to cross the ocular-, nasal-, oromucosal-, and vaginal mucosal barriers emphasizing advanced liquid drug delivery systems and the progress made toward clinical translation as a platform for future transmucosal liquid-based dosage form development.