大豆甾醇糖苷及两亲性聚乙二醇对阳离子脂质体细胞转染与膜各向异性的影响

目的：考察不同脂质体材料对阳离子脂质体细胞转染率和脂质体膜流动性的影响。方站：合成美国FDA认可应用于人体给药的阳离子材料3β-N-(N’，N’-二甲基胺乙基)胺基甲酰基]胆固醇(3βN-(N’，N’-dimethy-laminoethane)carbamoyl]cholesterl，DC-chol)；以荧光素钠(fluorescein sodium，SF)为荧光标记物，二棕榈酰磷脂酰胆碱(dipalmibylphosphatidylcholine，DPPC)、二油酰磷脂酰乙醇胺(dioleoylphosphatidylethanolamine，DOPE)和胆固醇(cholesterol，ch)为辅佐膜材，分别制备DPPC／ch／DC-chol阳离子脂质体、DOPE/ch／DC-chol阳离子脂质体及大豆甾醇糖苷(soybean-derlved sterylglucoside，SG)或聚乙二醇-二硬脂酰磷脂酰乙醇胺(polyethylene glycol-dis-tearoylphosphatidylethanolamine，PEG-DSPE)表面修饰的阳离子脂质体，并制备DPPC/ch组成的中性脂质体。以HepG2 2．2．15为细胞模型观察不同脂质体处方对细胞转染率的影响；通过荧光偏振法考察不同脂质材料对脂质体膜流动性的影响。结果：DC-chol能显著增加脂质体对SF的包封率(从0．64％到的74．84％)、细胞转染率(从1．83％到32．29％)及脂质体膜的流动性。在阳离子脂质体处方中加入SG能显著提高阳离子脂质体的包封率(从52．60％到63．37％)、细胞转染率(从20．18％到47．48％)及脂质体膜的流动性；PEG-DSPE可促进阳离子脂质体的细胞转染(从20．18％到28．17％)。结论：DC-chol和SG能显著提高脂质体的细胞转染率和脂质体膜的流动性；PEG-DSPE能促进阳离子脂质体的细胞转染。

Influence of soybean-derived sterylglucoside and amphipathic polyethylene glycol on the cellular delivery and anisotropy of different cationic liposomes

OBJECTIVE: To investigate the influences of different lipids on cellular delivery and fluidity of liposome membrane of cationic liposome. METHODS: The 3 beta N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-chol), a cationic lipid was synthesized, which is approved by FDA. Using fluorescein sodium (SF) as a model material, dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE) and cholesterol (ch) as help lipids, the DPPC/ch/DC-chol cationic liposomes, DOPE/ch/DC-chol cationic liposome and soybean-derived sterylglucoside (SG) or polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) modified cationic liposomes were prepared, respectively. The neutral liposome DPPC/ch was also prepared. HepG2 2.2.15 was selected as an in vitro cell culture assay model to investigate the cellular delivery of different liposomes. The influences of different lipids on the fluidity of liposome membranes were investigated with the technique of fluorescence polarization. RESULTS: It is showed that the DC-chol has significant influences on the incorporation efficiencies (from 0.64% to 74.84%), cellular delivery (from 1.83% to 32.29%) and the fluidity of liposome membrane; SG can significantly increase the incorporation efficiency (from 52.60% to 63.37%), cellular delivery (from 20.18% to 47.48%) and fluidity of liposome membrane; PEG-DSPE can enhance the cellular delivery of cationic liposome (from 20.18% to 28.17%). CONCLUSION: DC-chol and SG can significantly increase the cellular delivery and fluidity of liposome membrane, PEG-DSPE can enhance the cellular delivery of cationic liposome.