title: Polyaspartamides as water-soluble drug carriers. Part 1: Antineoplastic activity of ferrocene-containing polyaspartamide conjugates.
abstract: BACKGROUND
  Numerous detrimental side effects and/or lack of water-solubility of anticancer drugs often prove dose-limiting in chemotherapy. Water-soluble polymeric drug carriers may overcome/minimise many of these limitations.
  
  
  METHODS
  Aspartic acid polymers to which ferrocene-containing antineoplastic agents are covalently bound, were tested for cytotoxicity against murine EMT-6 cancer cells. Cell survival was measured by means of the colorometric 3-(4,5-dimethylthiazol-2-yl)-diphenyltertrazolium bromide assay.
  
  
  RESULTS
  The 90% lethal dosage of pure 3-ferrocenylbutanoic acid is 452 microg/mL LD90 for the polymeric derivative, expressed in terms of 3-ferrocenylbutanoic acid content, is only 65 microg/ml. A polymer structural effect in drug activity was evident: longer side chains linking drugs to polymer backbones enhanced drug activity. Drug activity is also enhanced if drug modifications (to enable drug anchoring) resulted in a lower ferrocenyl reduction potential.
  
  
  CONCLUSIONS
  The effectivity of antineoplastic drugs may be enhanced by covalently anchoring them on suitable biodegradable water-soluble polymeric drug carriers.
authors.affiliation: Department of Chemistry, University of the Orange Free State, Bloemfontein, Republic of South Africa. Swartsjc@cem.nw.uovs.ac.za
authors.forename: J C
authors.initials: JC
authors.lastname: Swarts
authors.forename: D M
authors.initials: DM
authors.lastname: Swarts
authors.forename: D M
authors.initials: DM
authors.lastname: Maree
authors.forename: E W
authors.initials: EW
authors.lastname: Neuse
authors.forename: C
authors.initials: C
authors.lastname: La Madeleine
authors.forename: J E
authors.initials: JE
authors.lastname: Van Lier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology*; D000075163:Metallocenes; D051379:Mice; D008956:Models, Chemical; D014407:Tumor Cells, Cultured; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005296:Ferrous Compounds; D000075163:Metallocenes; D014867:Water; C004998:ferrocene