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)mV,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。
Abstract
OBJECTIVE To synthesize a novel cationic lipid,N,N-dimethyl-[N′,N′-di-(stearoyl-1-ethyl)] 1,3-diaminopropane (DMSP),and evaluate its feasibility as methotrexate(MTX) carrier. METHODS DMSP and phosphatidylcholine were employed to prepare liposomes by reverse phase evaporation method,and then MTX was entrapped by physical mixing. The entrapment efficiency was determined by ultracentrifugation,and its release ratio was evaluated by dialysis. The morphology of liposomes was observed under transmission electron microscope. The average diameter and Zeta potential were determined by laser particle size analyzer. MTT test was used to evaluate the cytotoxicity of liposomes as drug carrier and the inhibition of cancer cells growth. RESULTS The obtained liposomes showed regular shape and uniform size,with a mean Zeta potential of +(36.26±4.77)mV and average diameter of 120 nm. The liposomes had low hemolytic activity and cytotoxicity. With the help of DMSP the cationic liposomes achieved a very high entrapment efficiency for the hydrophilic drug MTX (91.50±1.02)%. The inhibition of the MTX liposomes on cancer cells growth was much higher than that of MTX solution. CONCLUSION DMSP is a novel cationic lipid with low cytotoxicity and high entrapment efficiency,which has a great application potential in drug delivery system.
关键词
N /
N-二甲基-[N′ /
N′-双(十八酰氧基-1-乙基)]1 /
3-丙二胺 /
阳离子脂质体 /
甲氨蝶呤
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Key words
N /
N-dimethyl-[N′ /
N′-di-(stearoyl-1-ethyl)] 1 /
3-diaminopropane /
cationic liposome /
methotrexate
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中图分类号：
R944
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参考文献
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