Soluble polymers as carriers of cis-platinum

Abstract

Cis-dichlorodiammineplatinum(II) (cis-DDP) was complexed to various macromolecular carriers and the complexes were characterized for their in vitro pharmacological activity and in vivo therapeutic benefits. Complexes of DNA were highly stable and therefore inactive both in vitro and in vivo. Complexes of proteins (immunoglobulin and bovine serum albumin) contained low amounts of complexed drug, and were consequently ineffective. Complexes of hyaluronic acid were highly unstable and their activity and toxicity were similar to those of the free drug, both in vitro and in vivo. Complexes of carboxymethyl dextran were moderately stable, and were as active in vitro as the free drug. At an optimal molecular size of the carrier (around 40,000) the complexes were superior to the free drug, as they were highly effective, less toxic and of a wider therapeutic range. Complexes of the antineoplastic copolymer divinyl ether-maleic anhydride were relatively stable, poorly active in vitro but their therapeutic activity was superior to that of drug or carrier alone. Complexes of poly(glutamic acid) or poly(aspartic acid) were relatively stable, and demonstrated low in vitro activity. However, these complexes exerted a wide therapeutic range of activity due to their low toxicity, and thus were of the highest therapeutic efficacy of all complexes studied.