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

Abstract

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.

Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: human and animal health

“…via modification of the expression level or the activity of enzymes involved in the xenobiotic metabolism such as the cytochromes P450). It is also important to consider potential interference of nanomaterials with media components of in vitro test systems (see Section 7.3.1) (Cornu et al., 2018).…”

A Comprehensive Assessment of Hepatotoxicity Induced by Engineered Nanoparticles- A Review

“…This study concluded that glutathione metabolism and oxidative stress are amongst the principal causes of SiNP induced hepatotoxicity [108]. SiNPs influence CYP 450 both in rat and human hepatocytes [109]. In addition to apoptosis, SiNPs can induce pyroptosis through NLRP3 inflammasome activation which is caused by mesosporous sil-flammatory cytokines.…”

Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA

“…PLGA is one of the most widely used polymers for preparing nanoparticles by this method and different types of end-groups or functionalization are commercially available. When PLGA with carboxylic end groups is used, negatively charged nanoparticles form spontaneously in absence of surfactants [51]. Here, the ester-capped PLGA was chosen to form the polymeric matrix of hybrid nanoparticles, because its end groups are neutral, which prevents any risk of electrostatic interaction with positively charged siRNA Lpx [41].…”