Utilization of Quinolone Drugs as Monomers:  Characterization of the Synthesis Reaction Products for Poly(norfloxacin diisocyanatododecane polycaprolactone)

A broad spectrum antimicrobial agent, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (norfloxacin), has been successfully incorporated as a monomer into a polyurethane backbone structure via a three-step polymerization of norfloxacin, diisocyanatododecane (DDI), and polycaprolactone diol (PCL). The reaction was catalyzed by dibutyltin dilaurate and carried out in dimethyl sulfoxide. The sequential order of monomer feeding had a strong influence on the polymerization behavior and final polymer structure. In the preferred reaction scheme norfloxacin is initially reacted with DDI to form an oligomer. This is followed by a second reaction where PCL is introduced in order to produce a drug polymer chain with higher molecular weight and degradable segments. Cross-linking of urea linkages between the norfloxacin and DDI segments was a particular concern and was minimized by feeding PCL into the reaction system immediately following the completion of the first step. Chain extension by 1,4-butanediol or ethylenediamine was shown to be an effective approach for increasing the molecular weight of the polymers.