Mucus epithelia in the intestine, lung, mouth, eye, and vagina provide an effective and essential barrier against the entry of pathogens and toxins. Since these epithelia are readily accessible from outside the body, they also represent valuable sites for drug delivery. Here, we propose to continue our bioengineering studies of the ability of molecules and cells to function in and penetrate the mucus coat that protects these tissues. The ultimate goal is to use our findings to design methods for the controlled delivery of antibodies (Ab) or vaccinogens (Vg) directly to a mucus epithelium: Ab to provide passive immunoprotection, Vg to stimulate active immunoprotection. Specifically, biocompatible polymeric controlled release devices will be designed to continuously deliver macromolecules, like Ab and Vg, to mucus layers over a thirty day period. The present studies will focus on a) the distribution and bioavailability of AB and Bg molecules to penetrate and function in mucus samples collected at different times during the menstrual cycle. Since macrophages and other phagocytic cells can transport pathogens and molecules across mucus layers, the ability of phagocytic cells to crawl in mucus will studied, as well as the ability of mucus and Ab to interfere with phagocyte migration and adhesion to epithelial tissues. Mathematical methods will be used to correlate our in vitro and in vivo results, to enhance the value of in vitro methods for optimizing devices for use in vivo. All of the information collected from these basic studies will be used to design improved controlled release polymers for the localized and extended delivery of Ab or Vg to mice and rabbits. Finally, these polymers will be used to test the efficacy of controlled delivery for sustained protection against infectious disease (vaginal herpes virus infections) or unwanted pregnancy (immunocontraception).
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