The effect of the preservative propyl paraben (PPB) on the phase transition and dynamics of dipalmitoyl phosphatidic acid (DPPA)-buffer (pH 7.4/9.3) vesicles has been studied using DSC and (H-1 and P-31) NMR. These investigations were carried out with DPPA dispersion in both multilamellar vesicular (MLV) and unilamellar vesicular (ULV) forms. DSC results indicate that the mechanism by which PPB interact with the DPPA vesicles is similar in MLV and ULV and is independent of pH of the buffer used to form the dispersion. However, for a given concentration of PPB, the perturbation in DPPA bilayer is more when the dispersion is prepared in buffer pH 7.4. PPB affected both the thermotropic phase transition and the molecular mobility of the DPPA membrane. In the presence of PPB, the gel to liquid crystalline phase transition temperature (T-m) of the DPPA vesicles decreases hence increases membrane fluidity due to reduced headgroup-headgroup interaction. For all concentrations, the PPB molecules seem to get intercalated between the polar groups of the phospholipids with its alkyl chain penetrating into the co-operative region. At high PPB concentration, additional transitions are observed whose intensity increases with increasing PPB concentration. The large enthalpy values obtained at high PPB concentration suggest that presence of PPB makes the DPPA bilayer more ordered (rigid). The interesting finding obtained with MLV is that the stable gel phase of DPPA-buffer (pH 9.3/7.4) system in the presence of high PPB concentration becomes a metastable gel phase, this metastable gel phase on equilibration at 25 degrees C or when cooled to -20 degrees C transforms to a stable crystalline phase(s). The intensity of this new phase(s) increases with increasing PPB concentration. However, the transition temperatures of these new phases are not significantly changed with increasing PPB concentration. The effect of inclusion of cholesterol in the PPB-free and PPB-doped DPPA dispersion was also studied. (c) 2007 Elsevier Inc. All rights reserved.