Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units

We synthesized a water soluble glycol chitosan polymer grafted with cholesterol through substitution reaction, and the polymer was applied to form a polymer-liposome complex (PLC). According to dynamic light scattering (DLS) and transmission electron microscope (TEM) characterization, the diameter of the PLC was about 100 nm and the morphology was similar to the plain liposome. The cholesterol group can induce the polymer backbone to attach to the surface of the liposome membrane and the integration cability of the glycol chitosan-cholesterol (GCC) was characterized by laser confocal scanning microscope (LCSM). The zeta potential of the liposome containing negative charged phospholipid was - 23.2 mV. With integration of the glycol chitosan-cholesterol, the zeta potential significantly increased to - 1.78 mV, which indicated that the attached water-soluble polymer can shield the surface charge of the membrane. By encapsulating fluorescent molecules in the liposome or mixing fluorescent phospholipid during the lipid preparation process, fluorescence resonance energy transfer (FRET) experiment was introduced to test the stability of the PLC. Charge-induced liposome fusion occurred by adding positively charged ions or liposome into negatively charged liposome solution. The PLC has shown the ability to resist the fusion process which can keep the integrity and monodispersity of the liposome. However, the plain liposome was observed in aggregates visible to the naked eyes after adding hetero-charged ions in several minutes. The FRET variation results indicated that the addition of the GCC can slow down the hetero-charged liposome fusion process. In addition, the PLC can also protect against the liposome leakage induced by surfactant, which resulted from synergistic effect of polymer multiple-units. Incubated with 20% FBS under 37 degrees C, the PLC showed well stability in 3 days, while the PDI and the size of the plain liposome were increased obviously during incubation. The preparation process of this polymer-liposome complex strategy is simple and fast, and it has shown good stability in in vitro experiments. This system has potential applications in long circulation drug delivery. [GRAPHICS] .