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- W2950204068 abstract "Recent studies indicated obvious impacts of nano-carriers on cytochrome P450 enzymes (CYP450s) in vitro, but the effects in vivo are still unknown. In the present research, mPEG2k-PCLx micelles with different length of hydrophobic block (2000–10,000 Da) were intravenously administrated into rats for 14 days to evaluate the sub-chronic influences in the metabolic function of hepatic CYP450s. Although CYP1A1/B2 was susceptible to mPEG2k-PCLx micelles compared with other CYP isoenzymes, induction was mainly observed and varied with micelle type, administration dose, and CYP isoform. Interestingly, mPEG2k-PCL3.5k micelles at 5 mg/kg increased the activity of CYP1A2, CYP2B1, CYP2C6, CYP2C11, and CYP3A1/2 while mPEG2k-PCL5k micelles only induced the latter three enzymes at 75 mg/kg. The mRNA expression of corresponding CYPs was mostly up-regulated by mPEG2k-PCL3.5k micelles whilst less effect in protein level except for CYP3A1/2. Moreover, mPEG2k-PCL3.5k micelles could affect the pharmacokinetic properties of phenacetin (CYP1A2), tolbutamide (CYP2C6), omeprazole (CYP2C11), and midazolam (CYP3A1/2) with a decrease of 19.6% in Cmax, 20.5% in AUC0-t, 31.6% in AUC0-t, and 40.1% in Cmax at 5 mg/kg, respectively (P < 0.05 or P < 0.01). These results unveiled nano-DDS might be involved in nanocarrier-drug interaction by intervening in the activity of CYP450s." @default.
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- W2950204068 date "2019-09-01" @default.
- W2950204068 modified "2023-10-18" @default.
- W2950204068 title "The sub-chronic impact of mPEG2k-PCLx polymeric nanocarriers on cytochrome P450 enzymes after intravenous administration in rats" @default.
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- W2950204068 doi "https://doi.org/10.1016/j.ejpb.2019.06.017" @default.
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