Liposomes as cyclosporin A carriers: ESR study of cyclosporin A interaction with 1,2-dimyristoyl-sn-3-phosphatidylglycerol liposomest

Abstract

In order to study the interaction of cyclosporin A (CsA) with phosphatidyl-glycerol liposomes, thermally induced changes of 1,2-dimyristoyl-sn-3-phosphatidylglycerol (DMPG) liposomes and DMPG liposomes containing CsA were studied by electron spin resonance (ESR) spectroscopy using 5-, 7-, 10-, 12-or 16- nitroxide stearic acid (NO-SA) as spin probes. All liposomes were purified by Sepharose 4B column chromatography and the molar ratio of [¹⁴C]DMPG/[³H]CsA in these liposomes was found to be 31.1 ± 0.6. ESR spectroscopy established that the gel-to-liquid crystalline phase transition of DMPG liposomes occurred sharply at 22°C, shifted significantly to 26–34°C in the presence of CsA, detected with 5-, 7-, 10- and 12-NO-SA probes. Furthermore, transitions at 23°C and 31°C were detected with 16-NO-SA probe in the same liposomes containing CsA. It was concluded that CsA interacts with both the polar head group region and the entire hydrocarbon region of DMPG and must be embedded in the hydrophobic region of liposomes.