Silymarin loaded liposomes for hepatic targeting: In vitro evaluation and HepG2 drug uptake
Silymarin loaded liposomes for hepatic targeting: In vitro evaluation and HepG2 drug uptake
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DOI：
10.1016/j.ejps.2013.06.012
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发表时间：
2013-10-09
影响因子：
4.6
通讯作者：
Yliperttula, Marjo
中科院分区：
文献类型：
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作者：
Elmowafy, Mohammed;Viitala, Tapani;Yliperttula, Marjo
水飞蓟素具有保肝作用，可用于治疗各种肝脏疾病，但其口服产品的生物利用度非常差。为了克服其口服生物利用度差的问题，我们制备了适合肠胃外给药的负载水飞蓟素的肝靶向脂质体。脂质体制剂由氢化大豆磷脂酰胆碱和胆固醇组成，含有或不含二硬脂酰磷酸乙醇胺-(聚乙二醇)-2000以及不同量的β-谷甾醇β-D-葡萄糖苷(Sito-G)作为肝靶向部分。增加脂质体中 Sito-G 的量，药物包封率逐渐降低，从约 70% 降至约 60%；仍然显示出有希望的药物封装效率。在非聚乙二醇化脂质体中添加 Sito-G 明显影响其药物释放曲线和血浆蛋白相互作用，而对聚乙二醇化脂质体则没有影响。在所有研究的脂质体制剂中，Sito-G 比例为 0.17 M 的非聚乙二醇化脂质体表现出最高的细胞药物吸收率，达 37.5%。聚乙二醇化脂质体的最高细胞药物摄取率为 18%，这是通过添加 0.17 和 0.33 M 比例的 Sito-G 实现的。本研究中药物递送效率最高的脂质体制剂显示出约12.7%的溶血活性，并且在4℃和室温下在含有1.5%聚山梨醇酯80的20 mM HEPES缓冲液（pH 7.4）中储存后可稳定至少2个月。这些结果表明，本工作中制备的含有 Sito-G 的脂质体具有肝靶向能力，并且它们是将水飞蓟素递送至肝脏的有希望的候选者。 (C) 2013 Elsevier B.V. 保留所有权利。
Silymarin has hepatoprotective properties and is used in treatment of various liver diseases, but its bioavailability from oral products is very poor. In order to overcome its poor oral bioavailability we have prepared silymarin loaded hepatic targeting liposomes suitable for parenteral administration. The liposomal formulations were composed of hydrogenated soy phosphatidylcholine and cholesterol with or without distearoylphosphoethanolamine-(polyethyleneglycol)-2000 and various amounts of beta-sitosterol beta-D-glucoside (Sito-G) as the hepatic targeting moiety. Increasing the amount of Sito-G in the liposomes gradually decreased drug encapsulation efficiencies from similar to 70% to similar to 60%; still showing promising drug encapsulation efficiencies. Addition of Sito-G to non-PEGylated liposomes clearly affected their drug release profiles and plasma protein interactions, whereas no effect on these was seen for the PEGylated liposomes. Non-PEGylated liposomes with 0.17 M ratio of Sito-G exhibited the highest cellular drug uptake of 37.5% for all of the studied liposome formulations. The highest cellular drug uptake in the case of PEGylated liposomes was 18%, which was achieved with 0.17 and 0.33 M ratio of added Sito-G. The liposome formulations with the highest drug delivery efficacy in this study showed hemolytic activities around 12.7% and were stable for at least 2 months upon storage in 20 mM HEPES buffer (pH 7.4) containing 1.5% Polysorbate 80 at 4 degrees C and room temperature. These results suggest that the Sito-G containing liposomes prepared in this work have hepatic targeting capability and that they are promising candidates for delivering silymarin to the liver. (C) 2013 Elsevier B.V. All rights reserved.