Pharmacokinetics, Tissue Distribution and Excretion of Ag2S Quantum Dots in Mice and Rats: the Effects of Injection Dose, Particle Size and Surface Charge.

Abstract

We systematically investigated the effects of injection dose, particle size and surface charge on the pharmacokinetics, tissue distribution and excretion of Ag2S quantum dots (Qds) in rats and mice. Three different doses of Ag2S Qds with similar size and composition were administrated to rats and mice. The effect of size and surface charge was investigated with the injection of three sizes (5, 15 and 25nm) of Ag2S Qds possessing similar surface charge, as well as 5nm Qds with a positive surface charge. Results indicated that pharmacokinetics and biodistribution of Ag2S Qds were strongly dose, particle size and surface charge dependent. By increasing the dose from 0.5 to 4.0mg/kg, mean residence time (MRT) and apparent volume of distribution at steady state (Vss) were increased while clearance (CL) was decreased. Qds with a negative surface charge had significantly larger MRT and Vss values than positively charged particles, but their CL was about 50% lower than that of positively charged ones. By increasing Qds size from 5 to 25nm, CL was increased while MRT and AUC were decreased. This study establishes comprehensive principles for the rational design and tailoring of Ag2S Qds for biomedical applications. Graphical Abstract The effects of injection dose, particle size and surface charge on pharmacokinetics and tissue distribution of Ag2S Qds after intravenous injection into rats and mice were investigated.