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目的合成新型阳离子脂质N,N-二甲基-[N’,N’-双(硬脂酰基-1-乙基)]1,3-丙二胺(DMSP),考察其作为阳离子脂质膜材的应用前景。方法以二甲胺、1,3-溴氯丙烷、二乙胺和硬脂酸为原料通过3步反应合成N,N-二甲基-[N’,N’-双(硬脂酰基-1-乙基)]1,3-丙二胺,以N,N-二甲基-[N’,N’-双(硬脂酰基-1-乙基)]1,3-丙二胺和大豆磷脂S100(SPC)为膜材采用逆相蒸发法制备脂质体,并将甲氨蝶呤载入脂质体内,用超速离心法测定药物包封率,透析法测定其体外释放。利用透射电镜观察脂质体形态,激光粒度仪测定其粒径和Zeta电位,红细胞溶血实验测定空白脂质体的溶血性,噻唑蓝比色法测定空白脂质体的细胞毒性及含药脂质体的肿瘤细胞增长抑制率。结果由N,N-二甲基-[N’,N’-双(硬脂酰基-1-乙基)]1,3-丙二胺和大豆磷脂S100制备的阳离子脂质体形态规整,Zeta电位为+(36.26±4.77)m V,平均粒径约为120 nm;且该空白脂质体对红细胞溶血性较小,基本没有细胞毒性;利用该阳离子脂质体能有效地提高水溶性药物甲氨蝶呤的包封率,最高包封率为(91.50±1.02)%;载药脂质体对肿瘤细胞生长抑制作用远高于甲氨蝶呤水溶液。结论 N,N-二甲基-[N’,N’-双(硬脂酰基-1-乙基)]1,3-丙二胺制备的脂质体是一种高效低毒的药物载体,在药物传递系统中具有较强的应用前景。
OBJECTIVE To synthesize novel cationic lipid N, N-dimethyl- [N ’, N’-bis (stearoyl-1-ethyl)] 1,3-propanediamine (DMSP) Film application prospects. Methods The N, N-dimethyl- [N ’, N’-bis (stearoyl-1 -ethyl)] 1,3-propanediamine with N, N-dimethyl- [N ’, N’-bis (stearoyl-1-ethyl) Phospholipid S100 (SPC) was used to prepare liposomes by reverse phase evaporation, and methotrexate was loaded into liposomes. The drug entrapment efficiency was determined by ultracentrifugation and the in vitro release was determined by dialysis. The morphology of liposomes was observed by transmission electron microscopy. The particle size and Zeta potential were measured by laser particle size analyzer. The hemolysis of blank liposomes was determined by erythrocyte hemolysis assay. The cytotoxicity of blank liposomes and drug-containing lipids Tumor cell growth inhibition rate of the body. Results Cationic liposomes prepared from N, N-dimethyl- [N ’, N’-bis (stearoyl-1-ethyl)] 1,3-propanediamine and soya lecithin S100 were regular in morphology and Zeta The potential was + (36.26 ± 4.77) m V, the average particle size was about 120 nm; and the blank liposomes had less hemolytic activity on erythrocytes and had almost no cytotoxicity. The cationic liposomes could effectively increase the water-soluble drug A The entrapment efficiency of methotrexate was (91.50 ± 1.02)%. The inhibitory effect of drug-loaded liposomes on the growth of tumor cells was much higher than that of methotrexate. Conclusion The liposome prepared from N, N-dimethyl- [N ’, N’-bis (stearoyl-1-ethyl)] 1,3-propanediamine is a kind of high efficient and low toxicity drug carrier, In the drug delivery system has a strong application prospects.