{"title":"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","authors":"Xin Song, Minglan Zheng, Heping Hu, Lei Chen, Shuzhe Wang, Zhao Ding, Guangyi Fu, Luyao Sun, Liyuan Zhao, Ling Zhang, Bohua Xu, Yunliang Qiu","doi":"10.1007/s13318-024-00884-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>The pharmacokinetics of [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-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, [<sup>14</sup>C]-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. [<sup>14</sup>C]-HY-088 and [<sup>55</sup>Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 μCi/kg, and their metabolism was observed.</p><p><strong>Results: </strong>In the pharmacokinetic study, [<sup>55</sup>Fe]-HY-088 reached the maximum observed concentration (C<sub>max</sub>) at 0.08 h in the low- and medium-dose groups of SD rats. [<sup>14</sup>C]-HY-088 reached C<sub>max</sub> at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-HY-088 increased with increasing dose. In the tissue distribution study, [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-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 <sup>55</sup>Fe from [<sup>55</sup>Fe]-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 [<sup>14</sup>C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively.</p><p><strong>Conclusions: </strong>Following single intravenous administration of [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-HY-088 in SD rats, rapid absorption was observed. Both [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [<sup>55</sup>Fe]-HY-088 is mainly present in the carcass, whereas the <sup>14</sup>C-labeled [<sup>14</sup>C]-HY-088 shell PAA is eliminated from the body mainly through the urine.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic Study of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles HY-088 in Rats.\",\"authors\":\"Xin Song, Minglan Zheng, Heping Hu, Lei Chen, Shuzhe Wang, Zhao Ding, Guangyi Fu, Luyao Sun, Liyuan Zhao, Ling Zhang, Bohua Xu, Yunliang Qiu\",\"doi\":\"10.1007/s13318-024-00884-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>The pharmacokinetics of [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-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, [<sup>14</sup>C]-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. [<sup>14</sup>C]-HY-088 and [<sup>55</sup>Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 μCi/kg, and their metabolism was observed.</p><p><strong>Results: </strong>In the pharmacokinetic study, [<sup>55</sup>Fe]-HY-088 reached the maximum observed concentration (C<sub>max</sub>) at 0.08 h in the low- and medium-dose groups of SD rats. [<sup>14</sup>C]-HY-088 reached C<sub>max</sub> at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-HY-088 increased with increasing dose. In the tissue distribution study, [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-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 <sup>55</sup>Fe from [<sup>55</sup>Fe]-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 [<sup>14</sup>C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively.</p><p><strong>Conclusions: </strong>Following single intravenous administration of [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-HY-088 in SD rats, rapid absorption was observed. Both [<sup>55</sup>Fe]-HY-088 and [<sup>14</sup>C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [<sup>55</sup>Fe]-HY-088 is mainly present in the carcass, whereas the <sup>14</sup>C-labeled [<sup>14</sup>C]-HY-088 shell PAA is eliminated from the body mainly through the urine.</p>\",\"PeriodicalId\":11939,\"journal\":{\"name\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13318-024-00884-6\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Drug Metabolism and Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13318-024-00884-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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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