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-solubili ty of anticancer drugs often prove dose-limiting in chemotherapy. Water-sol uble polymeric drug carriers may overcome/minimise many of these limitation s. Materials and Methods: Aspartic acid polymers to which ferrocene-contain ing antineoplastic agents are covalently bound, were tested for cytotoxicit y 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 mug/ml. LD90 for the polymeric derivative, expressed in terms of 3-fer rocenylbutanoic acid content, is only 65 mug/mL. A polymer structural effec t in drug activity was evident: longer side chains linking drugs to polymer backbones enhanced drug activity. Drug activity is also enhanced if drug m odifications (to enable drug anchoring) resulted in a lower ferrocenyl redu ction potential. Conclusions: The effectivity of antineoplastic drugs may b e enhanced by covalently anchoring them on suitable biodegradable water-sol uble polymeric drug carriers.