Association and Phase Behavior of Cholic Acid-Modified Dextran and Phosphatidylcholine Liposomes

Abstract

The interaction between liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)) and a hydrophobically modified water-soluble polymer (HMP; a bile acid-modified dextran) has been investigated by isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC), combined with turbidity measurement and cryogenic scanning electron microscopy (cryo-SEM). The thermodynamic information on the association (enthalpy of interaction, enthalpy of transition of mixed vesicles to mixed micelle-like aggregates) was obtained from ITC. Further, the phase behavior for the system could be derived from the ITC measurements, and be confirmed by turbidity and cryo-SEM. The effect of cholic acid (CA) side groups on the ordered arrangement of DMPC bilayers was studied by DSC, by following the changes they induce in the gel-to-liquid crystalline liposome phase transition. The DSC results were in excellent agreement with the interpretation proposed for the ITC results. The morphology of the aggregates, as characterized by cryo-SEM, is in line with the proposed aggregate morphologies.