T. Peleg-shulman et al., Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance, BBA-BIOMEMB, 1510(1-2), 2001, pp. 278-291
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.