Preparation and characterization of a lovastatin-loaded protein-free nanostructured lipid carrier resembling high-density lipoprotein and evaluation of its targeting to foam cells.
Preparation and characterization of a lovastatin-loaded protein-free nanostructured lipid carrier resembling high-density lipoprotein and evaluation of its targeting to foam cells.
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DOI：
10.1208/s12249-011-9668-0
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发表时间：
2011-12
影响因子：
3.3
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Gu X;Zhang W;Liu J;Shaw JP;Shen Y;Xu Y;Lu H;Wu Z
本研究旨在研究一种类似高密度脂蛋白（HDL）的非蛋白质纳米结构脂质载体（NLC）是否可以将疏水性抗动脉粥样硬化药物洛伐他汀递送到泡沫细胞。通过纳米沉淀/溶剂扩散法制备了负载洛伐他汀的NLC（LT-NLC）。通过将LT-NLC与天然HDL孵育制备LT-NLC-载脂蛋白（LT-NLC-apo）。从粒径、Zeta电位、形态、包封率和结晶行为等方面对LT-NLC的理化参数进行了表征。通过在存在或不存在极低密度脂蛋白（VLDL）和脂肪酶的情况下将LT-NLC-apo与RAW 264.7巨噬细胞衍生的泡沫细胞模型孵育，证明了靶向行为和机制。结果表明，LT-NLC为实心球形或椭圆形，平均粒径为13.8 ± 2.2 nm，Zeta电位为−29.3 ± 0.2 mV，包封率为96.2 ± 1.3%。巨噬细胞对LT-NLC-apo的吞噬作用显著低于LT-NLC（p < 0.01），提示LT-NLC-apo在体内可能逃避巨噬细胞的识别。当LT-NLC-apo与含有VLDL和脂肪酶的转染泡沫细胞孵育时，摄取增加两倍。这些结果表明，类似HDL的非蛋白质NLC可能是将亲脂性抗动脉粥样硬化药物递送到泡沫细胞的有用工具，并且可以通过VLDL受体途径增强摄取。
This study was designed to investigate whether a non-protein nanostructured lipid carrier (NLC) resembling high-density lipoprotein (HDL) could deliver a hydrophobic anti-atherogenic drug, lovastatin, to foam cells. Lovastatin-loaded NLC (LT-NLC) was prepared by a nanoprecipitation/solvent diffusion method. The LT-NLC-apoprotein (LT-NLC-apo) was prepared by incubating LT-NLC with native HDL. The physicochemical parameters of LT-NLC were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and crystallization behavior. Targeting behavior and mechanism were demonstrated by the incubation of LT-NLC-apo with a RAW 264.7 macrophage-derived foam cell model in the presence or absence of very-low-density lipoprotein (VLDL) and lipase. The results showed that LT-NLC was solid spherical or oval in shape with an average diameter of 13.8 ± 2.2 nm, zeta potential of −29.3 ± 0.2 mV and entrapment efficiency of 96.2 ± 1.3%. Phagocytosis studies showed that uptake of LT-NLC-apo by macrophages was significantly lower than LT-NLC (p < 0.01), suggesting that LT-NLC-apo could possibly escape recognition from macrophages in vivo. The uptake was increased twofold when LT-NLC-apo was incubated with transfected foam cells containing VLDL and lipase. These results indicated that non-protein NLC resembling HDL could be a useful tool to deliver lipophilic anti-atherogenic drugs to foam cells, and that uptake could be enhanced by the VLDL receptor pathway.
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影响因子：
1.9
作者：
MARANHAO, RC;CESAR, TB;MESQUITA, CH
通讯作者：
MESQUITA, CH
影响因子：
2.9
作者：
FRY, DW;WHITE, JC;GOLDMAN, ID
通讯作者：
GOLDMAN, ID
影响因子：
8.7
作者：
Escary, JL;Choy, HA;Schotz, MC
通讯作者：
Schotz, MC
影响因子：
15
作者：
Frias, JC;Williams, KJ;Fayad, ZA
通讯作者：
Fayad, ZA
影响因子：
37.8
作者：
Hiltunen, TP;Luoma, JS;Ylä-Herttuala, S
通讯作者：
Ylä-Herttuala, S