Abstract:

An enzymatic synthesis and chemical polymerization strategy has been used to prepare ketoprofen polymeric prodrug with glucose pendant. Polymerizable ketoprofen vinyl ester(KVE) and glucose derivative(6-O-vinylsuccinoyl-D-glucose)(VSUG) were obtained. Then, polymeric prodrugs of ketoprofen were synthesized by the two kinds of monomers with different molar ratios(n(KVE)∶n(VSUG): 1∶1, 1∶2, 2∶1, 4∶1) through free radical reaction using AIBN as the initiator. The structures of products were confirmed by IR, NMR, and GPC. The results suggested that the molecular weight decreased and drug loading capacity increased as the ratio of KVE in the feed raised. In vitro release behavior of these copolymers was investigated in PBS(pH=7.4) at 37 ℃. Contrast to the parent drug, the outcome demonstrated that the polymeric prodrug could effectively prolong the drug release rate. And the release rate of ketoprofen from polymeric prodrugs increased with the raising of glucose in the polymeric prodrug. Furthermore, investigations of the drug release profiles and kinetics suggested that the drug release gave a good fit to firstorder kinetic model.

Key words: copolymer, ketoprofen, saccharide, enzyme-catalyzed synthesis, dynamic release, drug delivery