Čes. slov. farm. 2003, 52(6):299-305

Solubilization of Unilamellar Egg Yolk Phosphatidylcholine Liposomes by N-Alkyl-N,NdimethylamineN-oxides

A. Hrubšová¹, J. Karlovská¹, F. Devínsky², I. Lacko², P. Balgavý¹

¹ Katedra fyzikálnej chémie liečiv Farmaceutickej fakulty Univerzity Komenského, Bratislava

² Katedra chemickej teórie liečiv Farmaceutickej fakulty Univerzity Komenského, Bratislava

The solubilization of extruded (100 nm) unilamellar egg yolk phosphatidylcholine (EYPC) liposomesby a series of N-alkyl-N,N-dimethylamine N-oxides (CnNO, n=10-14 carbon atoms in the alkylsubstituent) was studied using turbidimetry. The solubilizing concentration of CnNO (cS) wasestimated as the CnNO concentration causing the half-maximum decrease in turbidance. From thelinear cS dependence on EYPC concentration, the lipid - aqueous phase molar partition coefficient(Kp) and theCnNO:EYPCmolar ratio in theCnNO+EYPCaggregates (nL:nEYPC) at cS wereobtained:Kp=82±25 and nL:nEYPC =0,70±0,20 for C10NO, Kp=507±215 and nL:nEYPC =0,60±0,16 for C12NO,and Kp=12357±93 and nL:nEYPC =1,13±0,01 for C14NO. The value of Gibbs free energy of CnNOalkyl methylene group transfer from the aqueous to the lipid phase calculated from the Kpdependence on n is -1,2±0,2 RT (R=gas constant, T=absolute temperature), within the experimentalerror being the same as -1,026±0,006 RT obtained from the critical micellar concentrations ofCnNO.The increased value of nL:nEYPC for C14NO is caused by the decreased hydrophobic mismatch ofCnNO and EYPC hydrocarbon chain lengths. This mismatch results in a structural defect in thebilayer hydrophobic core, the primary cause of bilayer destabilization and solubilization.

Keywords: solubilization; liposome; bilayer; N-alkyl-N,N-dimethylamine N-oxide; phosphatidylcholine

Published: June 1, 2003  Show citation