Mucus epithelia in the intestine, lung, mouth, eye, and vagina provide an effective and essential barrier against the entry of pathogens and allergens. Since these tissues are easy to access from outside the body, they also represent attractive sites for drug delivery. Here, we propose a bioengineering study of the ability of molecules and cells to penetrate mucus layers. Our ultimate goal is to use our findings to design methods for the controlled delivery of antigens or antibodies directly to a mucus epithelium. Specifically, we will use biocompatible polymeric controlled release devices to continuously delivery molecules (including large molecular weight molecules like antibodies) to mucus layers. These devices will be studied in vitro (using unstirred cervical mucus in a capillary tube) and in vivo (using vaginal rings in female mice). Since the directed movement of phagocytic cells may provide an important mechanism for the translocation of molecules across mucus layers--as well as an important mechanism for pathogen entry into the body--we will also observe the ability of phagocytic cells to crawl in unstirred mucus layers and the effects of cell movement on molecular translocation. We will develop mathematical methods for analyzing our in vitro data and for correlating these results with in vivo experiments. Finally, we will use our understanding of cell and molecular transport in mucus secretions to design polymeric controlled release devices for passive immunization, be releasing a constant source of neutralizing antibodies into the mucus, and active immunization, by releasing a constant source of antigen into the mucus.
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