Preparation, characterization and inhibition on cytochrome P450 of gold and silver nanoparticles

Abstract

Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been recently used for clinical applications such as drug delivery, therapy and diagnostics. AuNPs and AgNPs were synthesized by using the chemical reduction method. In this study, the different stabilizers, citrate, polyethyleneimine (PEI) and polyvinylpyrrolidone (PVP), were used for gold nanoparticle synthesis. The average particle diameters of freshly prepared citrate, PEI and PVP stabilized AuNPs were 8.36 ± 1.94, 2.67 ± 1.04 and 5.05 ± 1.51 nm, respectively. The zeta potential of citrate, PEI and PVP stabilized AuNPs were -34.1 ± 1.3, 28.7 ± 2.2 and -3.3 ± 0.7 mV, in orderly. The size and zeta potential of AgNPs were 12.42 ± 2.48 nm and -43.6 ± 0.7 mV, respectively. The inhibitory effect of AuNPs and AgNPs was observed on human cytochrome P450 (CYP) isozymes, CYP1A2, CYP2C9, CYP2C19 and CYP3A4. The CYP inhibition was measured fluorometrically in 96-well plates. Citrate stabilized AuNPs had least inhibitory effect on all CYP isozymes compared to PEI and PVP stabilized AuNPs and AgNPs. AuNPs with positively charged stabilizer (PEI) exhibited the greatest inhibition on CYP with IC50 of 64.34 ± 0.05, 4.47 ± 0.03, 4.84 ± 0.01 and 16.89 ± 0.02 µM for CYP1A2, CYP2C9, CYP2C19 and CYP3A4, respectively. The potential of CYP inhibition seemed to depend upon the size and charge of the nanoparticles. The data from this study presented that citrate and PVP stabilized AuNPs caused low incidence of drug interaction. The mechanism of CYP inhibition and the effect of in vivo are suggested for further study.