We propose to develop novel oral drug delivery systems based on microspheres capable of increased bioadhesion with mucus. The bioadhesive phenomenon has been classically attributed to the use of polymers containing high concentrations of carboxyl groups (believed to form hydrogen bonds with mucus) and the presence of flexible polymer chains (thought to interpenetrate biological structures). We found that hydrophobic bioerodible thermoplastics exhibit very high bioadhesive -properties despite the lack of flexible polymer chains. The strongest example of thermoplastic bioadhesion occurred with polyanhydride copolymers. We believe the mechanism for adhesion is the high density of carboxylic groups exposed during degradation, and that other hydrophobic polymers with high concentrations of surface hydrophilic moieties will exhibit strong bioadhesive measurements. It is our hypothesis that performance of these novel drug delivery systems can be predicted by in vitro measurements of bioadhesive forces using four different methods: everted sac biaossay and measurements from CAHN, EMFT and contact angle studies. The four methods can be utilized to predict the performance of polymer systems in both rats and in larger animals (pigs). The end goal is to overcome the trans-species barrier in order to potentiate our drug delivery systems for use in humans. The significance of the proposed research is that it seeks to apply fundamental findings, derived from basic research into microsphere bioadhesion, to the development of new drug delivery systems and apply this to in vivo experiments in different species. The end goal is to move these novel drug delivery systems from research to clinical applications for treatment of diseases.