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.

MATERIALS AND

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.