Engineering drug delivery systems to overcome mucosal barriers for immunotherapy and vaccination

Mucosal surfaces protect our bodies from pathogens and external irritants using a system of biological barriers. Overcoming these barriers is a significant drug delivery challenge, particularly for immunotherapies that aim to modulate the local immune response. Reaching local lymphoid tissues and draining lymph nodes (LNs) requires crossing the mucus mesh, mucosal epithelium, and either targeting M cells covering lymphoid tissues or utilizing lymphatic transport that shuttles molecules and particulates from the periphery to the LN. We first highlight the barrier properties of mucus and mucosal epithelium, and the function of the mucosal immune system. We then dive into existing drug delivery technologies that have been engineered to overcome each of these barriers. We particularly focus on novel strategies for targeting lymphoid tissues, which has been shown to enhance immunotherapies and vaccinations, via directly targeting LNs, lymphatic vessels, and M cells that transport samples of mucosal content to the lymphoid tissues.