Pharmacokinetic Study of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles HY-088 in Rats

Abstract

Background and objective: HY-088 injection is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIOs) composed of iron oxide crystals coated with polyacrylic acid (PAA) on the surface. The purpose of this study was to investigate the pharmacokinetics, tissue distribution, and mass balance of HY-088 injection.

Methods: The pharmacokinetics of [⁵⁵Fe]-HY-088 and [¹⁴C]-HY-088 were investigated in 48 SD rats by intravenous injection of 8.5 (low-dose group), 25.5 (medium-dose group), and 85 (high-dose group) mg/100 μCi/kg. Tissue distribution was studied by intravenous injection of 35 mg/100 μCi/kg in 48 SD rats, and its tissue distribution in vivo was obtained by ex vivo tissue assay. At the same time, [¹⁴C]-HY-088 was injected intravenously at a dose of 25.5 mg/100 μCi/kg into 16 SD rats, and its tissue distribution in vivo was studied by quantitative whole-body autoradiography. [¹⁴C]-HY-088 and [⁵⁵Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 μCi/kg, and their metabolism was observed.

Results: In the pharmacokinetic study, [⁵⁵Fe]-HY-088 reached the maximum observed concentration (C_max) at 0.08 h in the low- and medium-dose groups of SD rats. [¹⁴C]-HY-088 reached C_max at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [⁵⁵Fe]-HY-088 and [¹⁴C]-HY-088 increased with increasing dose. In the tissue distribution study, [⁵⁵Fe]-HY-088 and [¹⁴C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes of both female and male rats. In the mass balance study conducted over 57 days, the radioactive content of ⁵⁵Fe from [⁵⁵Fe]-HY-088 was primarily found in the carcass, accounting for 86.42 ± 4.18% in females and 95.46 ± 6.42% in males. The radioactive recovery rates of [¹⁴C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively.

Conclusions: Following single intravenous administration of [⁵⁵Fe]-HY-088 and [¹⁴C]-HY-088 in SD rats, rapid absorption was observed. Both [⁵⁵Fe]-HY-088 and [¹⁴C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [⁵⁵Fe]-HY-088 is mainly present in the carcass, whereas the ¹⁴C-labeled [¹⁴C]-HY-088 shell PAA is eliminated from the body mainly through the urine.