ANTIMETASTATIC ACTIVITY OF NEOCARZINOSTATIN INCORPORATED INTO CONTROLLED RELEASE GELS OF CM-CHITIN

6-O-carboxymethyl chitin (CM-chitin), a water-soluble chitin derivative, was gelled in the presence of 15 to 30 mm iron (III) chloride. At the time of gel formation, a peptidic anticancer drug neocarzinostatin (NCS), was efficiently (> 50%) incorporated into the gel in the co-presence of 25 to 50 mm calcium chloride and iron (III) chloride. CM-chitin gel containing NCS was digested by lysozyme in vitro and NCS was released from the gel in both a time- and dose-dependent manner. In-vivo studies in mice showed that free NCS was rapidly cleared from the circulation. but NCS released from the gel was detectable in plasma even 48 h after the subcutaneous injection of the gel. Antimetastatic effects of the CM-chitin gel containing NCS were studied in the spontaneous pulmonary metastasis model using B16-BL6 melanoma; these results suggest that CM-chitin gels are useful as a sustained-release drug carrier.