Antitumor Activity of Chitosan and Chitin Immobilized 5-Fluorouracils through Hexamethylene Spacers via Carbamoyl Bonds

Abstract

To provide a macromolecular prodrug of 5-fluorouracil (5FU) with reduced side-effects, an affinity for tumor cells and exhibiting the high antitu mor activity, the covalent attachment of 5FU to chitosan and chitin through hexamethylene spacers via carbamoyl bonds was carried out. In vivo testing against p-388 lyphocytic leukemia in female CDF₁ mice by intraperitoneal in jection (i.p.) and the in vivo growth-inhibitory effect on Meth-A fibrosarcoma in SPF-C3H/He mice by subcutaneous injection (s.c.)/intravenous injection (i.v.) were evaluated. The effects of the degree of polymerization of chitosan and the degree of 5FU substitution per glucosamine unit on the prolongation of life were investigated. The chitosan-5FU and chitin-5FU conjugates exhibited high survival effects and chitosan-5FU conjugate showed significant growth- inhibitory effect on Meth-A fibrosarcoma. These chitosan-5FU and chitin-5FU conjugates did not display any acute toxicity in the 800 mg/kg dose range.