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洛伐他汀仿生纳米脂质体的制备、体外靶向性及家兔体内药代动力学

陈瑶, 谷晓

陈瑶, 谷晓. 洛伐他汀仿生纳米脂质体的制备、体外靶向性及家兔体内药代动力学[J]. 中国药科大学学报, 2014, 45(5): 544-550. DOI: 10.11665/j.issn.1000-5048.20140507
引用本文: 陈瑶, 谷晓. 洛伐他汀仿生纳米脂质体的制备、体外靶向性及家兔体内药代动力学[J]. 中国药科大学学报, 2014, 45(5): 544-550. DOI: 10.11665/j.issn.1000-5048.20140507
CHEN Yao, GU Xiao. Preparation of bionic lovastatin-loaded nanostructured lipid carrier and its in vitro targeting and in vivo pharmacokinetics in rabbits[J]. Journal of China Pharmaceutical University, 2014, 45(5): 544-550. DOI: 10.11665/j.issn.1000-5048.20140507
Citation: CHEN Yao, GU Xiao. Preparation of bionic lovastatin-loaded nanostructured lipid carrier and its in vitro targeting and in vivo pharmacokinetics in rabbits[J]. Journal of China Pharmaceutical University, 2014, 45(5): 544-550. DOI: 10.11665/j.issn.1000-5048.20140507

洛伐他汀仿生纳米脂质体的制备、体外靶向性及家兔体内药代动力学

Preparation of bionic lovastatin-loaded nanostructured lipid carrier and its in vitro targeting and in vivo pharmacokinetics in rabbits

  • 摘要: 以洛伐他汀(LT)为模型药物,用高密度脂蛋白(HDL)脂质组分制备洛伐他汀纳米脂质体(LT-NLC),考察了LT-NLC的形态、粒径、Zeta电位、包封率以及结晶行为。将LT-NLC体外和HDL孵育获得载脂蛋白(apo)制备LT-NLC-apo(代表NLC体内起主要作用的组分),评价其体外逃避巨噬细胞吞噬和靶向到泡沫细胞的能力,并对其进行了家兔体内的药代动力学研究。结果表明,LT-NLC为球形或者椭圆形的粒子,粒径(14.6±2.0)nm,Zeta电位(-32.3±0.4)mV,包封率(96.2±1.3)%。体外研究显示内源性的LT-NLC-apo能逃避巨噬细胞的吞噬并靶向到泡沫细胞,药代动力学数据进一步证明LT-NLC可有效逃避吞噬,延长体内循环时间。不含蛋白的仿HDL组分的NLC有望成为传递亲脂性抗动脉粥样硬化药物到泡沫细胞的有效工具。
    Abstract: Lovastatin-loaded nanostructured lipid carrier(LT-NLC)was prepared by lovastatin(LT)and the lipid components of high density lipid protein(HDL). The physicochemical parameters of LT-NLC were characterized in terms of morphology, particle size, Zeta potential, entrapment efficiency, and crystallization behavior. The LT-NLC-apoprotein(LT-NLC-apo), represented effective form in vivo, was prepared by incubating LT-NLC with native HDL. The escaping ability from macrophage cells phagocytosis and targeting effect to foam cells were evaluated, and the pharmacokinetic behavior was invesigated on rabbits. The results showed that LT-NLC was solid spherical or oval in shape with an average diameter of(14. 6±2. 0)nm, Zeta potential of(-32. 3±0. 4)mV and entrapment efficiency of(96. 2±1. 3)%. Phagocytosis studies showed that endogenous LT-NLC-apo can escape phagocytosis and target to foam cells. Pharmacokinetic data also prove that LT-NLC can escape phagocytosis effectively and extend the circulating time in vivo. The study indicated that non-protein NLC-resembling HDL could be a useful tool to deliver lipophilic anti-atherogenic drugs to foam cells.
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  • 刊出日期:  2014-10-24

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