人参果皂苷前体阳离子脂质体的制备及体外释放研究
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摘要
目的优化人参果皂苷前体阳离子脂质体的处方,并对其体外释放、细胞毒性进行研究。方法采用乙醇注入法、冷冻干燥法制备人参果皂苷前体阳离子脂质体,用Box-Behnken试验设计优化脂质体处方,扫描电镜观察脂质体的形态,透析法考察脂质体的体外释放度,MTT法考察脂质体细胞毒性。结果 Box-Behnken优化后脂质体最优处方为:DOTAP质量329.2 mg,蛋黄卵磷脂质量192.2 mg,胆固醇质量332.2 mg,脂质体包封率达到65.29%,复溶后的脂质体粒径分布集中,形态均一呈球形;体外释放实验结果表明脂质体具有缓释效果,能够延长作用时间;脂质体对细胞的毒副作用较小,具有较好的细胞安全性。结论人参果皂苷前体阳离子脂质体与原料药相比具有延缓释放,增强口服生物利用度等特点。
Objective To optimize the formulation of Ginseng fruit saponins procationic liposomes and study on the release and cytotoxicity in vitro.Methods Ginseng fruit saponins procationic liposomes were prepared by the ethanol injection and freeze-drying methods,using Box-Behnken experimental design to optimize the liposomal formulation,using electron microscope to observe morphology of liposomes,using dialysis method for in vitro release study,and MTT method for investigating liposome cytotoxicity.Results The optimal liposome formulation after the Box-Behnken optimization is DOTAP of 329.2 mg,egg phosphatidylcholine of 192.2 mg,cholesterol of 332.2 mg,liposome encapsulation efficiency of 65.29%,after reconstitution the particle size of liposomes was concentrated with a uniform spherical shape; in vitro release test results show that the liposomes have sustained-release effect,to extend the duration of action; liposomes on cell toxicity is small,with better cell security.Conclusion Compared with Ginseng fruit saponins,the procationic liposomes can smoothly release drug and enhance oral bioavailability.
Objective To optimize the formulation of Ginseng fruit saponins procationic liposomes and study on the release and cytotoxicity in vitro.Methods Ginseng fruit saponins procationic liposomes were prepared by the ethanol injection and freeze-drying methods,using Box-Behnken experimental design to optimize the liposomal formulation,using electron microscope to observe morphology of liposomes,using dialysis method for in vitro release study,and MTT method for investigating liposome cytotoxicity.Results The optimal liposome formulation after the Box-Behnken optimization is DOTAP of 329.2 mg,egg phosphatidylcholine of 192.2 mg,cholesterol of 332.2 mg,liposome encapsulation efficiency of 65.29%,after reconstitution the particle size of liposomes was concentrated with a uniform spherical shape; in vitro release test results show that the liposomes have sustained-release effect,to extend the duration of action; liposomes on cell toxicity is small,with better cell security.Conclusion Compared with Ginseng fruit saponins,the procationic liposomes can smoothly release drug and enhance oral bioavailability.
引文
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[3]孙彦君,陈辉,郝志友,等.人参果化学成分研究[J].中药材,2014,37(8):1387-1390.
[4]林红梅,杨利民,韩梅,等.人参药效成分合成与调控机制研究进展[J].人参研究,2013,25(4):42-46.
[5]曹智,张燕娣,许永华,等.人参有效成分及其药理作用研究新进展[J].人参研究,2012,24(2):43.
[6]李晶,戴雨霖,郑飞,等.人参皂苷的口服吸收及体内转化[J].中国生物制品学杂志,2014,27(12):1633-1636.
[7]王健.人参皂苷Re对心血管系统的药理作用概述[J].黑龙江科技信息,2015(11):94.
[8]何晓玮,赵燕敏,包强,等.纳米载体提高难溶性药物口服生物利用度的研究进展[J].国际药学研究杂志,2011,38(3):212-215.
[9]刘洋,张振中,邵彦江,等.载基因纳米阳离子脂质体前体制剂的制备及性质研究[J].中国新药杂志,2010(1):72-75.
[10]陈伟光,刘源岗,王士斌,等.阳离子脂质体共载基因与化疗药物用于癌症治疗的研究进展[J].药学学报,2012(8):986-992.
[11]Zhong Z R,Zhang Z R,Liu J,et al.Characteristics comparison before and after lyophilization of transferrin modified procationic-liposome-protamine-DNA complexes(Tf-PLPD)[J].Archives of Pharmacal Research,2007,30(1):102-108.
[12]仲跻云,陈梁,杨肖斌.口服用前体脂质体的研究进展[J].药学与临床研究,2012,20(1):56-59.
[13]戎佩佩,宋金春.p H敏感前体阳离子脂质体的制备及瘤内分布研究[J].中国药学杂志,2012,47(6):444-447.
[14]王新春.白藜芦醇三个不同载体材料纳米口服给药系统的研究[D].四川大学,2007.
[15]冯杨,马玉坤,周华晨,等.新型脂质体的研究与应用[J].山东医药,2004,44(23):59-60.
[16]穆筱梅,梁世强.脂质体的制备方法及其研究进展[J].时珍国医国药,2008,19(7):1784-1786.
[17]Wang F,Chen L,Jiang S,et al.Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.[J].Journal of Liposome Research,2014,24(3):171-181.
[18]Shi J,Ma F,Wang X,et al.Formulation of liposomes gels of paeonol for transdermal drug delivery by Box-Behnken statistical design.[J].Journal of Liposome Research,2012,22(4):270-278.
[19]曲芯瑶,赵宏峰,弥宏,等.RP-HPLC测定人参果总皂苷中人参皂苷Re和人参皂苷Rd的含量[J].中国社区医师:医学专业,2014,30(1):5-6.
[20]何妍茜.人参果皂苷前体脂质体的研制[D].长春:吉林大学,2015.