Transmucosal drug delivery: prospects, challenges, advances, and future directions

Traditional administration routes have limitations including first-pass metabolism and gastrointestinal degradation for sensitive drugs (oral) and pain associated with parenteral injections, which also require trained personnel and refrigeration, making them expensive. This has increased interest in alternative routes, with mucosal surfaces being of high priority.

Mucosal routes include ocular, oral (buccal/sublingual), nasal and vaginal mucosae which avoid the limitations of the oral and parenteral routes. Though mucosal routes show great potential, they are still hindered by several barriers, especially for systemic absorption, resulting in the development of more advanced novel drug delivery systems to overcome these limitations and achieve therapeutic actions both locally and systemically, similar to or exceeding the oral route. This paper systematically reviews and compares the different mucosal routes, challenges, and recent advances in advanced novel drug delivery system design for emerging clinical challenges including the advent of large biological macromolecules (proteins, peptides, and RNA) for treatment and prevention of diseases. The review also focuses on current challenges and future perspectives.

Among the various transmucosal routes discussed, nose-to-brain drug delivery has the greatest translational potential to go beyond the current state of the art and achieve significant clinical impact for neurological diseases.