Polyethylene glycol (PEG)-capped gold nanoparticles (PEG-AuNPs) are of great interest for targeted drug and chemotherapy delivery due to their biocompatibility and ability to evade immune detection. However, repeated administration can trigger the accelerated blood clearance (ABC) phenomenon, reducing circulation time and altering pharmacokinetics. This study aimed to evaluate whether pretreatment with free PEG before PEG-AuNP administration could improve pharmacokinetic behavior and mitigate the ABC effect, compared to PEG-AuNPs alone. AuNPs were synthesized via the Turkevich-Frens method, PEGylated, and characterized using ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), zeta potential (ZP) analysis, and transmission electron microscopy (TEM). The PEG-AuNPs were spherical with a core diameter of 19.54 ± 1.758 nm. To assess the effect of free PEG, two groups of rats received an initial dose of PEG-AuNPs; both were given a second dose, but only the second group was pretreated with free PEG. Gold concentrations in plasma and organs were quantified using a validated inductively coupled plasma mass spectrometry (ICP-MS) method, and pharmacokinetic parameters were determined. The ABC index confirmed the ABC phenomenon when comparing the first and second PEG-AuNP doses. Unexpectedly, pretreatment with free PEG did not significantly affect pharmacokinetic parameters (Cmax, tmax, t0.5; p > 0.05) compared to non-pretreated animals. Notably, PEG-AuNP accumulation in the liver and spleen increased approximately six- to sevenfold and two- to threefold, respectively, after the second dose, consistent with ABC-associated organ uptake. In conclusion, under the current experimental conditions, pretreatment with free PEG before the second PEG-AuNP dose did not significantly mitigate the ABC phenomenon, indicating that additional strategies may be required to overcome immune recognition and enhance the pharmacokinetic performance of PEGylated nanocarriers.
Darweesh et al. (Tue,) studied this question.