超小型超顺磁性氧化铁纳米粒子 HY-088 在大鼠体内的药代动力学研究

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Xin Song, Minglan Zheng, Heping Hu, Lei Chen, Shuzhe Wang, Zhao Ding, Guangyi Fu, Luyao Sun, Liyuan Zhao, Ling Zhang, Bohua Xu, Yunliang Qiu
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引用次数: 0

摘要

背景和目的:HY-088注射液是一种超小型超顺磁性氧化铁纳米粒子(USPIOs),由表面包覆聚丙烯酸(PAA)的氧化铁晶体组成。本研究旨在探讨 HY-088 注射液的药代动力学、组织分布和质量平衡:方法:通过静脉注射 8.5(低剂量组)、25.5(中剂量组)和 85(高剂量组)mg/100 μCi/kg,对 48 只 SD 大鼠进行了[55Fe]-HY-088 和[14C]-HY-088 的药代动力学研究。通过静脉注射 35 mg/100 μCi/kg 研究了 48 只 SD 大鼠的组织分布情况,并通过体外组织测定获得了其在体内的组织分布情况。同时,以 25.5 mg/100 μCi/kg 的剂量向 16 只 SD 大鼠静脉注射[14C]-HY-088,并通过全身自显影定量研究其在体内的组织分布。以 35 mg/100 μCi/kg 的剂量向 24 只 SD 大鼠静脉注射[14C]-HY-088 和[55Fe]-HY-088,并观察其代谢情况:在药代动力学研究中,[55Fe]-HY-088 在低剂量组和中剂量组 SD 大鼠中 0.08 h 达到最大观察浓度(Cmax)。在三组 SD 大鼠中,[14C]-HY-088 在 0.08 小时达到 Cmax。55Fe]-HY-088和[14C]-HY-088的浓度-时间曲线下面积(AUC)随着剂量的增加而增加。在组织分布研究中,[55Fe]-HY-088 和 [14C]-HY-088 主要分布在雌性和雄性大鼠的肝脏、脾脏和淋巴结中。在为期 57 天的质量平衡研究中,[55Fe]-HY-088 中 55Fe 的放射性含量主要存在于雌性大鼠的躯体中,占 86.42 ± 4.18%,雄性大鼠占 95.46 ± 6.42%。雌性和雄性大鼠尿液中[14C]-HY-088的放射性回收率分别为(52.99±5.48)%和(60.66±2.23)%:在 SD 大鼠体内单次静脉注射 [55Fe]-HY-088 和 [14C]-HY-088 后,可观察到快速吸收。55Fe]-HY-088 和 [14C]-HY-088 主要分布于肝、脾和淋巴结。在代谢过程中,[55Fe]-HY-088 的放射性主要存在于胴体中,而 14C 标记的[14C]-HY-088 外壳 PAA 则主要通过尿液排出体外。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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