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INTERSPECIES DIFFERENCES IN CYTOCHROME P450 ACTIVITY OF HEPATOCYTES EXPOSED TO PLGA AND SILICA NANOPARTICLES: AN IN VITRO AND IN VIVO INVESTIGATION

Abstract

The nanomedicines represent a promising approach in the treatment and the 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 on the detoxification function of the liver remains unclear. The present study consists in 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 culture 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.

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Publication details

The article was received on 09 Jan 2018, accepted on 02 Feb 2018 and first published on 07 Feb 2018


Article type: Paper
DOI: 10.1039/C8NR00226F
Citation: Nanoscale, 2018, Accepted Manuscript
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    INTERSPECIES DIFFERENCES IN CYTOCHROME P450 ACTIVITY OF HEPATOCYTES EXPOSED TO PLGA AND SILICA NANOPARTICLES: AN IN VITRO AND IN VIVO INVESTIGATION

    R. Cornu, N. Rougier, Y. Pellequer, A. Lamprecht, P. Hamon, R. Li, A. Béduneau and H. Martin, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR00226F

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