AN ADHESIVE DRUG-DELIVERY SYSTEM BASED ON K99-FIMBRIAE

The principle of an enhanced gastrointestinal (GI) absorption of substances based on close contact with epithelial cells was used for the construction of a drug delivery system. The colonization of the small intestine by Escherichia coli strains is mediated by cell surface antigens called fimbriae, which enable bacteria to adhere to the brush border of epithelial cells. A special fimbriae antigen (K99) was isolated from an E. coli strain harbouring the fimbriae-encoding plasmid pRI9906. The functionality of isolated fimbriae was tested by a haemagglutination assay with equine erythrocytes, which represent the same K99-receptor-structures like GI-epithelial cells. The adherence ability of an adhesive drug delivery system such as neutralized polyacrylic acid (PAA) could be improved by the covalent binding of K99-fimbriae. Affinity of the matrix-bound fimbriae to their receptor could be confirmed with equine erythrocytes, which migrate through a K99-PAA-gel ten times slower than through the same gel without fimbriae. Such a fimbriae-mediated bioadhesive drug delivery system could lead to enhanced drug absorption.