Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance

Extensive scientific efforts are directed towards finding new and improved platinum anticancer agents. A promising approach is the encapsulation of ci splatin in sterically stabilized, long circulating, PEGylated 100 nm liposo mes. This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows excellent stability in plasma and has a longer circulation time, gre ater efficacy and lower toxicity than much free cisplatin. However, so far, the physicochemical characterization of STEALTH cisplatin has been limited to size distribution, drug-to-lipid ratio and stability. Information on th e physical state of the drug in the liposome aqueous phases and the drug's interaction with the liposome membrane has been lacking. This study was aim ed at filling this gap. We report a multinuclear NMR study in which several techniques have been used to assess the physical nature of cisplatin in li posomal formulations and if and to what extent the drug affects the liposom e phospholipids. Since NMR detects only the soluble cisplatin in the liposo mes and not the insoluble drug, combining NMR and atomic absorption data en ables one to determine how much of the encapsulated drug is soluble in the intraliposomal aqueous phase. Our results indicate that almost all of the c isplatin remains intact during the loading process, and that the entire lip osomal drug is present in a soluble form in the internal aqueous phase of t he liposomes, (C) 2001 Elsevier Science B.V. All rights reserved.