Poly(amidoamine) dendrimer-supported organoplatinum antitumour agents

While numerous water-soluble biocompatible polymers have been utilized for the construction of drug conjugates that offer significant advantages for drug delivery, poly(amidoamine) (PAMAM) dendrimers are superior in many ways for this purpose. They display nanoscale size, uniform shape, excellent water solubility, low toxicity and high surface functionality. In an attempt to circumvent the toxic side effects associated with the administration of organoplatinum drugs, a polymeric prodrug has been prepared from the treatment of a generation 4.5 PAMAM dendrimer with diaquo(1,2-diaminocyclohexane) platinum(II). A well-defined dendrimer-platinum conjugate containing 40 (1,2-diaminocyclohexane) platinum(II) units coordinated to the dendrimer surface via carboxylate groups is formed. This adduct is well behaved, water soluble, contains a high loading of platinum moieties and displays sustained release of active platinum species over a 24 h period under physiological conditions.