In recent years, clinical applications of recombinantly produced bioactive
proteins such as
cytokines have attracted attention. However, since these
recombinant proteins are rather unstable in vivo, their clinical use as therapeutic agents requires frequent administration at a high dosage. This regimen disrupts homeostasis and results in severe side effects. To overcome these problems, bioactive
proteins have been conjugated with water-soluble synthetic (WSS) polymeric carriers. Chemical modification of a
protein with a WSS polymeric carrier (bioconjugation) regulates tissue distribution, resulting in a selective increase in its desirable
therapeutic effects and a decrease in undesirable side effects. Among several drug delivery system (DDS) technologies, bioconjugation has been recognized as one of the most efficient methods for improving therapeutic potency of
proteins. However, for further enhancement of the therapeutic potency and safety of conjugated bioactive
proteins, more precise regulation of the in vivo behavior of each
protein is necessary for selective expression of its
therapeutic effect. Therefore, alternative WSS polymeric modifiers in which new functions such as targeting and controlled release of drugs can be added are required for further development of bioconjugated drugs. Recently, we have synthesized a novel polymeric
drug carrier,
poly(vinylpyrrolidone-co-dimethyl maleic anhydride) [PVD], which was a powerful candidate
drug carrier for
cancer therapy. In this review, we introduce useful information that enabled us to design polymeric
drug carriers and their application for
protein therapy.