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

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

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 (Cmax) at 0.08 h in the low- and medium-dose groups of SD rats. [14C]-HY-088 reached Cmax 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.

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Acknowledgements

The authors sincerely thank all members of QWBA and the tissue distribution studies team at InnoStar Bio-tech Nantong Co., Ltd. We also thank Sichuan Huiyu Seacross Pharmaceutical Co., Ltd. for providing the nano-innovative drugs for this experiment.

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Authors and Affiliations

  1. School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230013, China

    Xin Song, Luyao Sun & Liyuan Zhao

  2. InnoStar Bio-tech Nantong Co., Ltd., Nantong, 226133, China

    Xin Song, Lei Chen, Shuzhe Wang, Luyao Sun, Liyuan Zhao, Ling Zhang & Bohua Xu

  3. Sichuan Huiyu Seacross Pharmaceutical,. Co. Ltd, Sichaun, 610021, China

    Heping Hu, Zhao Ding & Guangyi Fu

  4. China Yangtze Delta Drug Advanced Research Institute, Nantong, 226133, China

    Xin Song, Luyao Sun & Liyuan Zhao

  5. Yangtze River Delta Center for Drug Evaluation and Inspection of NMPA, Shanghai, 201210, China

    Minglan Zheng

  6. China State Institute of Pharmaceutical Industry, Shanghai InnorStar Biotech Co., Ltd., Shanghai, 201203, China

    Yunliang Qiu

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  1. Xin Song
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Corresponding authors

Correspondence to Bohua Xu or Yunliang Qiu.

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Funding

This study was funded by Jiangsu Province New Drug One-Stop Efficient Non-clinical Evaluation Public Service Platform Construction BM2021002.

Conflicts of Interest

Minglan Zheng is an employee of Yangtze River Delta Center for Drug Evaluation and Inspection of NMPA. Heping Hu, Zhao Ding, and Guangyu Fu are employees of Sichuan Huiyu Seacross Pharmaceutical Co., Ltd. Lei Chen, Shuzhe Wang, Ling Zhang, and Bohua Xu are employees of InnoStar Bio-tech Nantong Co., Ltd. Yunliang Qiu is an employee of Shanghai InnorStar Biotech Co., Ltd. The other authors declare no competing interests.

Author Contributions

Xin Song: substantial contributions to the machine learning and interpretation of data for the work; drafting the work manuscript. Minglan Zheng: interpretation of data for the work; reviewing the manuscript. Heping Hu: interpretation of data for the work; reagent HY-088 injection was provided; reviewing the manuscript. Lei Chen: substantial contributions to conduct the machine learning and interpretation of data for the work. Shuzhe Wang: substantial contributions to conduct the machine learning and interpretation of data for the work; participated in research design. Zhao Ding: reviewing the manuscript; reagent HY-088 injection was provided; Guangyi Fu: reviewing the manuscript; reagent HY-088 injection was provided. Luyao Sun: interpretation of data for the work. Liyuan Zhao: interpretation of data for the work. Ling Zhang: substantial contributions to conduct the machine learning and interpretation of data for the work. Bohua Xu: substantial contributions to conduct the machine learning and interpretation of data for the work; interpretation of data for the work; reviewing the manuscript; final approval of the version to be published. Yunliang Qiu: reviewing the manuscript; final approval of the version to be published.

Availability of Data and Material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval

All animal experiments in this study were approved by the Institutional Animal Care and Use Committee of InnoStar Bio-tech Nantong Co., Ltd. Approval numbers: 2021-583 (2021.09.07), IACUC-2022-r-005a (2022.01.06), IACUC-2022-r-104 (2022.02.18), IACUC-2022-r-446 (2022.08.01), and IACUC-2022-r-626 (2022.10.17).

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Song, X., Zheng, M., Hu, H. et al. Pharmacokinetic Study of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles HY-088 in Rats. Eur J Drug Metab Pharmacokinet 49, 317–330 (2024). https://doi.org/10.1007/s13318-024-00884-6

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  • DOI: https://doi.org/10.1007/s13318-024-00884-6

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