Wednesday, December 17, 2008

European Journal of Pharmaceutical Sciences, Volume 34, Issues 2-3, 3 July 2008, Pages 140-148

Anticancer cisplatin interactions with bilayers of total lipid extract from pig brain: A 13C, 31P and 15N solid-state NMR study

Magnus Jensena and Willy Nerdal

Cisplatin (cis-diamminedichloroplatinum(II)) is used in chemotherapy and it is well established that cisplatin forms platinum-DNA adducts that initiate tumor cell death. Drawbacks are side effects such as neurotoxicity and cellular cisplatin resistance and it is possible that part of these effects are linked to cisplatin interaction with lipids and the phospholipid bilayer. 13C magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectra of total lipid extract from pig brain with and without cisplatin show that the phosphatidylserine (PS) carboxyl resonance disappears in presence of cisplatin and that a new resonance of similar intensity appears at 185.5 ppm. Thus, indicating cisplatin interaction with the PS head-group. Static and MAS 31P NMR spectra of lipid extract with and without cisplatin show that the phospholipids to a large extent reside in a bilayer environment in pure lipid extract, and that the presence of cisplatin promotes isotropic and/or hexagonal lipid phases.

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