Interspecies differences in the cytochrome P450 activity of hepatocytes exposed to PLGA and silica nanoparticles: an in vitro and in vivo investigation,Nanoscale

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Interspecies differences in the cytochrome P450 activity of hepatocytes exposed to PLGA and silica nanoparticles: an in vitro and in vivo investigation
Nanoscale ( IF 5.8 ) Pub Date : 2018-02-07 00:00:00 , DOI: 10.1039/c8nr00226f
Raphaël Cornu _{1,

2,

3,

4} , Nathalie Rougier _{4,

5,

6} , Yann Pellequer _{1,

2,

3,

4} , Alf Lamprecht _{1,

2,

3,

4,

7} , Paul Hamon _{1,

2,

3,

4} , Ruoya Li _{4,

5,

6} , Arnaud Beduneau _{1,

2,

3,

4} , Hélène Martin _{1,

2,

3,

4}

Affiliation

Nanomedicines represent a promising approach in the treatment and diagnosis of numerous disorders. The majority of the injected dose of nanoparticles (NPs) is sequestrated in the liver. Despite this hepatic tropism, the interaction of NPs with the detoxification function of the liver remains unclear. The present study consists of evaluating the impact of biodegradable poly(lactide-co-glycolide) (PLGA) and silica NPs on cytochrome P450 (CYP) activities. The effects of NPs were evaluated in vitro on human and rat hepatocytes in primary cultures and in vivo by intravenous injections in healthy rats. More than the physicochemical properties, the composition of NPs (organic, inorganic) dramatically influenced the detoxification function of the liver. Silica NPs modulated the CYP activity both in rat and human hepatocytes, in contrast to PLGA NPs. A CYP isoform-dependent effect was reported and the modulation of the metabolic hepatic activity was species-dependent. Human hepatocytes were sensitive to an exposure to PLGA NPs, whereas no marked effect was detected in rat hepatocytes. The in vitro data obtained in rat hepatocytes were correlated with the in vivo data. This study emphasizes the interest to set up relevant in vitro models using human hepatic cells to evaluate the hepatotoxicity of nanomedicines.

中文翻译：

的：在暴露于PLGA肝细胞和二氧化硅纳米粒子的细胞色素P450活性的种间差异在体外和体内调查

纳米药物是治疗和诊断多种疾病的有前途的方法。大部分注射剂量的纳米颗粒（NPs）被隔离在肝脏中。尽管存在这种肝向性，但是NP与肝的解毒功能之间的相互作用仍然不清楚。本研究包括评估可生物降解的聚（丙交酯-共-乙交酯）（PLGA）和二氧化硅NPs对细胞色素P450（CYP）活性的影响。NP的影响进行了评价在体外对原代培养物和人类和大鼠肝细胞在体内通过在健康大鼠中静脉注射。NPs（有机，无机）的组成不仅具有物理化学性质，还极大地影响了肝脏的排毒功能。与PLGA NP相比，二氧化硅NPs可以调节大鼠和人肝细胞中的CYP活性。据报道CYP异构体依赖性作用，并且代谢肝活性的调节是物种依赖性的。人肝细胞对暴露于PLGA NPs敏感，而在大鼠肝细胞中未检测到明显的作用。在体外在大鼠肝细胞得到的数据与相关的体内数据。这项研究强调了使用人肝细胞建立相关体外模型来评估纳米药物的肝毒性的兴趣。

更新日期：2018-02-07

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