Synthesis of 6‐O‐carboxymethylchitin immobilizing doxorubicins through tetrapeptide spacer groups and its enzymatic release behavior of doxorubicin in vitro

摘要

AbstractChitin is a non‐toxic biodegradable polysaccharide. 6‐O‐Carboxymethylchitin (CM‐chitin) is a water‐soluble chitin derivative. In order to provide a water‐soluble macromolecular prodrug of doxorubicin (DXR) reducing the side‐effects and exhibiting high antitumor activity, the fixation of DXRs to CM‐chitin through covalent bonds was carried out. Especially, a lysosomally digestible tetrapeptide (Gly‐Phe‐Leu‐Gly) was used as spacer groups between CM‐chitin and DXRs. In this paper, two kinds of conjugates, CM‐chitin/Gly‐Phe‐Leu‐Gly/DXR conjugate5having lysosomally digestible tetrapeptide spacer groups and CM‐chitin/C5/DXR conjugate6having pentamethylene spacer groups, were synthesized. The effect of introduction of the spacer groups on the release behavior of DXR from the conjugate was investigated. The conjugate5having tetrapeptide spacer groups showed a distinct increase in the release rate of DXR in the presence of the lysosomal enzyme cathepsin B at 37°C in vitro; however, the conjugate6did not s