Platinum Formulations as Anticancer Drugs Clinical and Pre-Clinical Studies

Nicholas      P. Farrell

Abstract

This review summarizes clinical and pre-clinical results on platinum anti-cancer drug formulations. A concise summary of the use of oxidation state to modulate cancer pharmacology is given for Pt(IV) complexes, distinct from the clinically used Pt(II) drugs. The chemistry of platinum drug formulation combines aspects of kinetics of active moiety release from nominally weak-binding ligands (bond cleavage from platinum-carboxylate and platinum-phosphate) in polymers and nanoparticles with pharmacological considerations of plasma distribution and cellular accumulation. The action of any molecular entity as a drug is influenced by its ADME profile - absorption, distribution, metabolism and excretion. The purpose of drug formulation is to alter any or all of these parameters with the ultimate goal of improving the efficacy and reducing side effects with the possibility to target drugs directly to the tumor site. The diverse array of approaches includes liposomes, polymers (not limited to peptides, dendrimers, biodegradable polymers, polysaccharides, and metallic nanoparticles). Functionalization of the surfaces of nanoparticles with antibodies or cellular surface recognition motifs may further target specific cancers.

Keywords: Platinum anti-cancer agents, formulation, polymer drug delivery, nanomedicine, platinum anti-cancer drug formulations, nanoparticles, plasma distribution and cellular accumulation, molecular entity, ADME profile, absorption, distribution, metabolism and excretion, efficacy, tumor site, recognition motifs, Chemotherapy, Platinum-based chemotherapy