Bacterial adhesins as a drug carrier: covalent attachment of K99 fimbriae to 6-methylprednisolone.

A bioadhesive drug delivery system based on the covalent attachment of a therapeutic agent to bacterial fimbriae is described. This approach involves the isolation of the fimbrium K99 as well as the covalent coupling of 6-methylprednisolone to this adhesin via a linker, especially designed to be cleaved by unspecific luminal esterases. Analysis of the conjugate showed a direct correlation between solubility and coupling extent. Under physiological conditions, a conjugate exhibiting a coupling extent higher than 0.8 (mol therapeutic agent/mol fimbrial subunit) demonstrated a dramatically decrease of solubility. Release of the drug could be verified by enzymatic cleavage of the conjugate in vitro. The adhesive properties of a drug delivery system containing 6-methylprednisolone and K99 fimbriae were assayed by a haemagglutination test.