Effect of Grafted Amphiphilic PVP-Palmityl Polymers on the Thermotropic Phase Behavior of 1,2 Dipalmitoyl- sn-glycero-3-phosphocholine Bilayer.
To better understand how grafted polymers interact with liposome membrane, a comparative study was conducted to investigate the influence of different chain length polyvinyl pyrrolidone-palmityl (PVP-p) conjugates on the thermotropic phase behavior of 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayer. Lipid-polymer dispersions were prepared by mixing DPPC and variable concentrations of PVP-p conjugates in chloroform. Hydration of lipids was performed at 50-55 degrees C after complete elimination of the organic solvent. Differential scanning calorimetry (DSC) was used to determine lipid miscibility and bilayer-polymer interactions. Particle size was determined by photon correlation spectroscopy. Increasing concentrations of 6 kDa PVP-p caused a shift of the main phase transition of DPPC at lower temperatures. At 9.1 mol% the DPPC phase pretransition (T(p)) is abolished. At 16.7 mol%, differential scanning calorimetry showed an endothermic phase transition at 24.9 degrees C. The enthalpy of this transition was twice as high compared to the main phase transition enthalpy of pure DPPC. Inclusion of more than 20 mol% of 6 kDa PVP-p resulted in a complete bilayer micellization. Qualitatively similar to the 6 kDa were the results obtained with the 12 kDa PVP-p conjugate. Increasing concentrations of 25 kDa PVP-p from 1 to 13 mol% resulted in a decrease of the main DPPC phase transition temperature. At 13 mol% the new molecular self-assembled structure as previously identified with the lower MW PVP-p conjugates also showed up at the DSC thermogram. However, in sharp contrast to the lower MW PVP-p conjugates, increasing the 25 kDa PVP-p content did not result in bilayer disruption; rather, it resulted in a bilayer stabilization. The consequences of the hydrophobically modified PVP interaction with the bilayer are considered negative with respect to the long-circulating properties of liposomes in the blood. Copyright 1999 Academic Press.
Savva
M
Departments of Pharmaceutical Sciences and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261
Torchilin
VP
Huang
L