Polyaspartamides as water-soluble drug carriers. Part 1: Antineoplastic activity of ferrocene-containing polyaspartamide conjugates.
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.
Swarts
J C
JC
Department of Chemistry, University of the Orange Free State, Bloemfontein, Republic of South Africa. Swartsjc@cem.nw.uovs.ac.za
Swarts
D M
DM
Maree
D M
DM
Neuse
E W
EW
La Madeleine
C
C
Van Lier
J E
JE
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
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005296:Ferrous Compounds; D000075163:Metallocenes; D014867:Water; C004998:ferrocene