Characterization of a novel polymeric prodrug of an antibacterial agent synthesized by mechanochemical solid‐state polymerization

Abstract

Polycrystalline methacryloyl monomers of the antibacterial drug nalidixic acid with an anhydride bond to the drug carboxyl group were prepared. The physicochemical properties of the synthesized vinyl monomer were characterized using X‐ray powder diffraction, thermal analysis, and polarized light microscopy measurements. Mechanochemical solid‐state polymerization of the resulting monomers was carried out to yield a novel polymeric prodrug. The in vitro hydrolysis behavior of the polymeric prodrug indicated that the release rate of drug from the polymeric prodrug was clearly dependent on the pH value of the hydrolysis solution. Moreover, sustained release of the drug at an almost constant rate for more than 10 hr was shown in both neutral and alkaline solutions. The results suggest that anhydride‐based polymeric prodrugs could be potentially useful in colon targeted drug delivery systems.

The mechanochemical synthesis of polymers

“…125,138 Continuing studies by Oprea in the 1980s and by Kuzuya in the 1990s covered many of the vinyl monomers known to undergo polymerisation (Scheme 1). 18 The adopted strategy was used to convert (meth)acrylates, 19,130,[139][140][141][142][143][144][145] (meth)acrylamides, 125,126,141,146 styrenes, 128,141,[147][148][149][150] and other structurally diverse vinyl monomers [149][150][151][152] into the corresponding polymers under solvent-free ball-milling conditions. Moreover, the copolymerisation of these monomers has also been investigated, 125,130,140,149,[153][154][155] as is discussed below.…”