[A design and development of novel polymeric prodrugs prepared by mechanochemical solid-state polymerization].

The mechanochemical polymerization of solid-state monomer was first reported in 1959. Nevertheless, relatively little work has been done. We reported the first in-depth study of the mechanochemical polymerization of specially synthesized solid-state monomers, methacryloyl derivatives of bioactive compounds including detailed mechanistic implications. There are many advantages for this reaction. One of the most striking properties observed in the resulting polymers is that these polymeric prodrugs are of very low heterogeneity (narrow molecular weight distribution) which is of great value in pharmaceuticals for highly functionalized polymeric prodrugs. Thus, the present reaction provides a novel and simple methodology for the syntheses of highly functionalized polymeric prodrugs through a totally dry process. The nature of drug release from many kinds of polymeric prodrugs prepared by mechanochemical polymerization was also investigated. The rate of drug release from the polymeric prodrugs can be controlled by the property of comonomer and the structure of spacer between the main chain of polymer and drug. Several applications of polymeric prodrugs (chemoembolization and hybrid polymeric prodrugs) were also described. We have carried out the mechanochemical polymerization in the presence of pharmaceutical aids to exploit the features of this reaction. If one takes the physicochemical property of pharmaceutical aids into consideration, novel composite polymeric prodrugs possessing a variety of rates of drug release can be synthesized simultaneously with mixing.