Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity
Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity
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DOI：
10.2147/ijn.s15160
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发表时间：
2011-01-01
影响因子：
8
通讯作者：
Mukherjee, Arup
中科院分区：
文献类型：
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作者：
Das, Suvadra;Roy, Partha;Mukherjee, Arup
水飞蓟素(Silymarin，Sm)是从水飞蓟中提取的多酚类化合物。它是一种抗氧化剂，传统上用作免疫刺激剂、肝脏保护剂和膳食补充剂。最近，Sm已被证明是一种有价值的化学预防和有用的抗肿瘤药物。然而，Sm的医学成功受到极低的水溶解度和相关的生物制药限制。SM黄酮木脂素也容易在肠道中被离子催化降解。因此，在扑热息痛过量这样的急性化学中毒情况下，已证实的Sm的抗肝毒性作用不能得到充分发挥。此外，肝脏再生所需的同步交付本身很难实现。这项工作旨在通过使用纳米技术来绕过Sm的固有限制。在聚乙烯醇稳定的Eudradit Rs100(R)聚合物(Rohm Pharma GmbH，Darmstadt，德国)中通过纳米沉淀法制备了Sm纳米颗粒(SMNP)。工艺参数优化后包封率为67.39%，平均粒径为120.37 nm，呈正态分布。在所有制剂中，SM从纳米粒中的释放都相当持久。在扑热息痛过量肝毒性模型中，SMNP对肝脏损伤有很强的保护作用。纳米颗粒没有记录动物死亡，即使在扑热息痛诱导的肝脏坏死后给予也是如此。对扑热息痛肝损伤的预防进展进行了跟踪，以使肝组织中谷胱甘肽的有效再生达到11.3mU/g/g。
Silymarin (Sm) is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps) were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100 (R) polymer (Rohm Pharma GmbH, Darmstadt, Germany). Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 mu mol/g in hepatic tissue due to Smnps.