Release behavior of ketoprofen from poly(acryloyl-L-proline methyl ester) gels having different crosslinked networks

In order to clarify the relationship between the crosslinked structure of thermo-responsive polymer and drug release profile, polymer gels based on acryloyl-L-proline methyl ester (A-ProOMe) were synthesized in a mixture of water and acetone by the following two methods: a simultaneously occurring process of radiation-induced polymerization and crosslinking without a crosslinker (self-bridging method), and radiation-induced polymerization in the presence of the crosslinker tetradecaethylene glycol dimethacrylate (crosslinker method). The pronounced gap in thermo-response between two A-ProOMe gels, with an apparent degree of crosslinking of 11 for 1-propanol, shows a different shrinking pattern in the initial stage of time. The gels, which were obtained with the self-bridging method and the crosslinker method, were kept constant at a swelling ratio of 17 in water at 0 degree C for all systems. However, those values fell to 0.5 and 4, respectively, at 10 min after the temperature was increased to 37 degrees C. The release mechanism of ketoprofen from two gel devices showed an anomalous (non-Fickian) transport, in which the release of ketoprofen with a low water-solubility could be directly related to the rapid release of water accompanying a gel shrinkage.