Biodistribution of trans-1,2-diammocyclohexane-trimellitato-platinum(II) attached to macromolecular carriers I. Poly(hydroxyethyl-d,l-asparagine) carrier

Abstract

Two types of macromolecular drug forms of the second generation piatinum antitumor drug 4-carboxy-phtalato-(trans, 1,2-diaminocyclohexane)platinum(II) (TMA) were prepared with non-biodegradable carriers derived from racemic poly (N 4 -substituted aspartamide): AN type was prepared from N-(2-hydroxyethyl) and AR type from N-(2-hydroxypropyl) derivative by acylation with trimellitato residues, thus yielding primary and secondary ester honds respectively. Plasma levels, urinary excretion and organ deposition of platinum were followed after administration into rats. When compared with free TMA both types of macromolecular forms showed a retardation effect in platinum pharma-cokinetics with the most pronounced differences using the AR type. Considering all possible biodegradable bonds in the polymeric drug forms the nature of the drug-polymer link seemed to play an important role in the kinetics of drug release as revealed by the differences between the AN and AR type.