AN ADHESIVE DRUG-DELIVERY SYSTEM BASED ON K99-FIMBRIAE

The principle of an enhanced gastrointestinal (GI) absorption of subst ances based on close contact with epithelial cells was used for the co nstruction of a drug delivery system. The colonization of the small in testine by Escherichia coil strains is mediated by cell surface antige ns called fimbriae, which enable bacteria to adhere to the brush borde r of epithelial cells. A special fimbriae antigen (K99) was isolated f rom an E. coli strain harbouring the fimbriae-encoding plasmid pRI9906 . The functionality of isolated fimbriae was tested by a haemagglutina tion assay with equine erythrocytes, which represent the same K99-rece ptor-structures like GI-epithelial cells. The adherence ability of an adhesive drug delivery system such as neutralized polyacrylic acid (PA A) could be improved by the covalent binding of K99-fimbriae. Affinity of the matrix-bound fimbriae to their receptor could be confirmed wit h equine erythrocytes, which migrate through a K99-PAA-gel ten times s lower than through the same gel without fimbriae. Such a fimbriae-medi ated bioadhesive drug delivery system could lead to enhanced drug abso rption.