Stabilized liposomes with phospholipid polymers and their interactions with blood cells

To stabilize a phospholipid liposome, addition of various water-soluble polymers into a liposomal aqueous suspension was investigated. The water-soluble polymers were poly(ethylene oxide) (PEO), poly(N-vinyl pyrrolidone) (PVPy) and poly2-methacryloyloxyethyl phosphorylcholine(MPC)], and polyMPC-co-n-butyl methacrylate(BMA)]. The gel–liquid crystal transition temperature (T_c) of the diparmitoylphosphatidylcholine (DPPC) liposome was not changed by addition of these polymers significantly. However, membrane fluidity of DPPC liposome treated with water-soluble polymers, which was measured with fluorescence probe, depended on the chemical structure of the water-soluble polymers. In the case of PEO and PVPy, the temperature dependence of membrane fluidity was the same as that of the original DPPC liposome, on the other hand, poly(MPC) and poly(MPC-co-BMA) induced a rise in the temperature where an increase in the membrane fluidity was observed. The release of carboxy fluorescein from the DPPC liposome was suppressed by the addition of the MPC polymers. The liposomes in the MPC polymer solution were stable compared with those in water when plasma was added into the suspension. Interactions with stabilized liposome with blood cells such as platelets and erythrocytes were evaluated. Activation of platelets in contact with liposome covered with poly(MPC) or poly(MPC-co-BMA) was less than PEO-stabilized liposome. On the other hand, no hemolysis of erythrocytes was observed when every polymer-treated liposome was added in the suspension of erythrocytes. Based on these results, the MPC polymers could interact with the liposome surface, adsorb on the liposomes and stabilize them, and had no adverse effect to the blood cells even when they were in a physiological environment.