Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified nanoliposomes.
Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified nanoliposomes.
复制标题
聚乙二醇化 G5 PAMAM 树枝状聚合物修饰纳米脂质体增强普罗布考的口服吸收
DOI：
10.1021/mp500388m
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发表时间：
2015-03-02
影响因子：
4.9
通讯作者：
Qi R
中科院分区：
文献类型：
--
作者：
Ma Q;Han Y;Chen C;Cao Y;Wang S;Shen W;Zhang H;Li Y;van Dongen MA;He B;Yu M;Xu L;Banaszak Holl MM;Liu G;Zhang Q;Qi R
普罗布考（PB）是一种抗氧化药物，临床上常用作降低血浆胆固醇水平的降脂药物。然而，这种药物的治疗效果受到其水溶性差和口服吸收效率低的负面影响。在这项研究中，采用PEG化的G5 PAMAM树状聚合物（G5-PEG）修饰的纳米脂质体来增加PB的水溶性、跨上皮转运和口服吸收。体外Caco-2细胞对G5-PEG修饰的PB-脂质体（PB-liposome/G5-PEG）的吸收机制研究结果表明，PB-liposome/G5-PEG的吸收促进作用与P-糖蛋白（P-gp）外排泵有关，而与小窝内吞途径无关。此外，在LDLR−/−高脂血症小鼠模型中体内评价了PB-脂质体/G5-PEG的血浆脂质浓度降低作用。与生理盐水对照组相比，PB-脂质体/G5-PEG能显著抑制高脂饮食引起的小鼠血浆总胆固醇（TC）和甘油三酯（TG）的升高。此外，其降脂作用和血浆药物浓度大于PB单独或商业PB片剂。我们的研究结果表明，PB-脂质体/G5-PEG显着增加PB的口服吸收，因此，显着提高其药效学作用。
Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration lowering drug to reduce blood plasma cholesterol levels in the clinic. However, the therapeutic effects of this drug are negatively impacted by its poor water solubility and low oral absorption efficiency. In this study, a PEGylated G5 PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water solubility, transepithelial transport, and oral absorption of PB. The uptake mechanism was explored in vitro in Caco-2 cells with the results suggesting that the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG) was related to P-glycoprotein (P-gp) efflux pump, but was independent of caveolae endocytosis pathways. Additionally, plasma lipid concentration lowering effects of PB-liposome/G5-PEG were evaluated in vivo in a LDLR−/− hyperlipidemia mouse model. Compared with saline treated group, treatment with PB-liposome/G5-PEG significantly inhibited the increase of plasma total cholesterol (TC) and triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid concentration lowering effects and plasma drug concentration were greater than PB alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG significantly increased the oral absorption of PB and therefore, significantly improved its pharmacodynamic effects.
研究设计和基本原理“与西洛舍唑和普罗库尔结合疗法对牙菌斑稳定和病变回归的协同作用（安全）”研究：一项双盲随机对照多中心临床试验。
影响因子：
2.5
作者：
Ko YG;Kim BK;Lee BK;Kang WC;Choi SH;Kim SW;Lee JH;Lee M;Honda Y;Fitzerald PJ;Shim WH;SECURE Investigators
通讯作者：
SECURE Investigators