Methods and compositions for enhancing the bioadhesive properties of

Abstract

Methods and compositions are provided for enhancing the bioadhesive properties of polymers used in drug delivery systems. The bioadhesive properties of a polymer are enhanced by incorporating an anhydride oligomer into the polymer to enhance the ability of the polymer to adhere to a tissue surface such as a mucosal membrane. Anhydride oligomers which enhance the bioadhesive properties of a polymer include oligomers synthesized from dicarboxylic acid monomers, preferably those found in Krebs glycolysis cycle, especially fumaric acid. The oligomers can be incorporated within a wide range of polymers including proteins, polysaccharides and synthetic biocompatible polymers. In one embodiment, anhydride oligomers can be incorporated within polymers used to form or coat drug delivery systems, such as microspheres, which contain a drug or diagnostic agent. The oligomers can either be solubilized and blended with the polymer before manufacture or else used as a coating with polymers over existing systems. The polymers, for example in the form of microspheres, have improved ability to adhere to mucosal membranes, and thus can be used to deliver a drug or diagnostic agent via any of a range of mucosal membrane surfaces including those of the gastrointestinal, respiratory, excretory and reproductive tracts.