Solubilization of Unilamellar Egg Yolk Phosphatidylcholine Liposomes by N-Alkyl-N,Ndimethylamine
N-oxides
HRUBŠOVÁ A., KARLOVSKÁ J., DEVÍNSKY F.1, LACKO I.1, BALGAVÝ P.
Katedra fyzikálnej chémie liečiv Farmaceutickej fakulty Univerzity Komenského, Bratislava 1 Katedra chemickej teórie liečiv Farmaceutickej fakulty Univerzity Komenského, Bratislava |
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Summary:
The solubilization of extruded (100 nm) unilamellar egg yolk phosphatidylcholine (EYPC) liposomes
by a series of N-alkyl-N,N-dimethylamine N-oxides (CnNO, n=10–14 carbon atoms in the alkyl
substituent) was studied using turbidimetry. The solubilizing concentration of CnNO (cS) was
estimated as the CnNO concentration causing the half-maximum decrease in turbidance. From the
linear 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 CnNO
alkyl methylene group transfer from the aqueous to the lipid phase calculated from the Kp
dependence on n is -1,2±0,2 RT (R=gas constant, T=absolute temperature), within the experimental
error 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 of
CnNO and EYPC hydrocarbon chain lengths. This mismatch results in a structural defect in the
bilayer hydrophobic core, the primary cause of bilayer destabilization and solubilization.
Key words:
solubilization – liposome – bilayer – N-alkyl-N,N-dimethylamine N-oxide –
phosphatidylcholine
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