Pharmacokinetics of polyethylene glycol (PEG)-capped gold nanoparticles in rats: impact of free PEG pre-administration

Abstract

Polyethylene glycol (PEG)-capped gold nanoparticles (PEG-AuNPs) are of great interest for targeted drug delivery and targeted delivery of chemotherapy due to their biocompatibility and ability to evade detection by the immune system. However, with repeated administration, the accelerated blood clearance (ABC) phenomenon can significantly reduce the circulation time of nanoparticles and alter key pharmacokinetic parameters. This study aims to evaluate whether pretreatment with free PEG before the administration of PEG-AuNPs can improve their pharmacokinetics and reduce the ABC effect, compared to the administration of PEG-AuNPs alone. AuNPs were synthesized using the Turkevich–Frens method, PEGylated, and characterized by ultraviolet–visible spectroscopy (UV–Vis), Dynamic light scattering (DLS), zeta potential (ZP) measurement, and transmission electron microscopy (TEM). The synthesized PEG-AuNPs were spherical with a core diameter of 19.54 ± 1.758 nm. To evaluate the effect of free PEG, two groups of rats were given an initial dose of PEG-AuNPs. Both groups then received a second dose, but only the second group was pretreated with free PEG before PEG-AuNPs administration. Gold concentrations in plasma and various organs were quantified using a validated inductively coupled plasma mass spectrometry (ICPMS) method, and pharmacokinetic parameters were subsequently determined. The ABC index confirmed the presence of the ABC phenomenon when comparing the first and the second doses of PEG-AuNPs. Unexpectedly, pretreatment with free PEG did not significantly alter the pharmacokinetic parameters (C max, t max, and t 0.5; p > 0.05) compared to the condition without pretreatment with free PEG. Accumulation of PEG-AuNPs in the liver and spleen increased by (6–7) and (2–3)-fold, respectively, after the administration of the second dose, compared to the first dose, which is consistent with the concept of the ABC phenomenon. In conclusion, under the experimental conditions of this study, the strategy of pretreatment with free PEG before the second dose did not significantly alleviate the effect of the ABC phenomenon in the context of PEG-AuNPs.