title: Contribution of chitosan and its derivatives to cancer chemotherapy.
abstract: The conjugates of some kinds of anticancer agents with chitin and chitosan derivatives display good anticancer effects with a decrease in the adverse effects of the original drug due to a predominant distribution into the cancer and a gradual release of free drug from the conjugates. For instance, doxifluridine and 1-beta-D-arabinofuranosylcytosine (Ara-C) were conjugated with chitosan via glutaric spacer, and the conjugates of Ara-C with chitosan, in particular, showed a good antitumour effect against P388-bearing leukemia model mice. Glycol-chitosan (G-Chi) was distributed mainly in the systemic circulation and the kidney after i.v. administration into normal mice, and retained long in the kidney. The therapeutic effect of the conjugates of mitomycin C (MMC) with G-Chi was not necessarily improved in comparison with that of the free drug, but toxic side-effects appeared to decrease with the conjugates. The conjugates of MMC with 6-O-carboxymethyl-chitin showed almost complete suppression of tumour growth at 10 mg eq. MMC/kg, though a lethal adverse effect was also observed. The conjugates of MMC with N-succinyl-chitosan showed good antitumour activities against various tumour models due to their predominant distribution into the tumour tissue and sustained-release characteristics, irrespective of water-insoluble and -soluble formulations. It is believed that the chitin and chitosan derivatives discussed in this review are good candidates for a polymeric drug carrier in cancer chemotherapy.
authors.affiliation: The Johns Hopkins University School of Medicine, Department of Radiology, Division of MR Research, Oncology Section, Baltimore, MD 21205, USA. yk-no.1@jcom.home.ne.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.forename: Hiraku
authors.initials: H
authors.lastname: Onishi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Machida
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002686:Chitin / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D048271:Chitosan / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D004354:Drug Screening Assays, Antitumor; D008954:Models, Biological
chemical_list: D000970:Antineoplastic Agents; C118638:glycol-chitosan; D002686:Chitin; D048271:Chitosan