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.
Bernkop-Schnürch
A
A
Institut für Pharmazeutische Technologie, Universität Wien, Vienna, Austria.
Gabor
F
F
Spiegl
P
P
D018830:Adhesins, Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D000954:Antigens, Surface / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins; D004337:Drug Carriers; D004912:Erythrocytes / Q000378:metabolism; D006386:Hemagglutination Tests; D006736:Horses; D066298:In Vitro Techniques; D008775:Methylprednisolone / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D018830:Adhesins, Escherichia coli; D000893:Anti-Inflammatory Agents; D000954:Antigens, Surface; D001427:Bacterial Toxins; D004337:Drug Carriers; C031429:K99 antigen; D008775:Methylprednisolone