Unmodified drug used as a material to construct nanoparticles: delivery of cisplatin for enhanced anti-cancer therapy.

The poor solubility of cisplatin (CDDP) often presents a major obstacle in the formulation of CDDP in nanoparticles (NPs) by traditional methods. We have developed a novel method for synthesizing CDDP NPs taking advantage of its poor solubility. By mixing two reverse microemulsions containing KCl and a highly soluble precursor of CDDP, cis-diaminedihydroplatinum (II), we have successfully formulated CDDP NPs with a controllable size (in the range of 12-75nm) and high drug loading capacity (approximately 80wt.%). The formulation was done in two steps. The pure CDDP NPs were first stabilized for dispersion in an organic solvent by coating with 1, 2-dioleoyl-sn-glycero-3-phosphate (DOPA). Both x-ray photoelectron spectroscopy and (1)H NMR data confirmed that the major ingredient of the DOPA-coated NPs was CDDP. After purification, additional lipids were added to stabilize the NPs for dispersion in an aqueous solution. The final NPs contain a lipid bilayer coating and are named Lipid-Pt-Cl (LPC) NPs, which showed significant antitumor activity both in vitro and in vivo. Thus, CDDP precipitate serves as the major material for assembling the novel NPs. This unique method of nanoparticle synthesis may be applicable in formulating other insoluble drugs.