99mTc-labeled, tofacitinib citrate encapsulated chitosan microspheres loaded in situ gel formulations for intra-articular treatment of rheumatoid arthritis

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-08-13 DOI:10.1002/ddr.22247
Merve Karpuz, Husniye Hande Aydin, Emre Ozgenc, Gulsah Erel-Akbaba, Evren Atlihan-Gundogdu, Zeynep Senyigit
{"title":"99mTc-labeled, tofacitinib citrate encapsulated chitosan microspheres loaded in situ gel formulations for intra-articular treatment of rheumatoid arthritis","authors":"Merve Karpuz,&nbsp;Husniye Hande Aydin,&nbsp;Emre Ozgenc,&nbsp;Gulsah Erel-Akbaba,&nbsp;Evren Atlihan-Gundogdu,&nbsp;Zeynep Senyigit","doi":"10.1002/ddr.22247","DOIUrl":null,"url":null,"abstract":"<p>Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize <sup>99m</sup>Tc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with <sup>99m</sup>Tc, the optimum radiolabeling condition was determined as 200 ppm SnCl<sub>2</sub> and 0.5 mg ascorbic acid, and both <sup>99m</sup>Tc-MS/TOFA-9 and <sup>99m</sup>Tc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22247","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22247","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc-MS/TOFA-9 and 99mTc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
99m锝标记的枸橼酸托法替尼包裹壳聚糖微球原位凝胶制剂,用于类风湿性关节炎的关节内治疗。
包括类风湿性关节炎在内的炎症性疾病是主要的健康问题。尽管临床上有不同的技术和药物可用于诊断和治疗该疾病,但有关放射性标记给药系统的新方法仍在研究之中。因此,本研究旨在设计、制备和表征用于关节内治疗的 99mTc 放射性标记和枸橼酸托法替尼胶囊化微球负载聚氧乙烯醚原位凝胶制剂。在九种不同的微球制剂中,MS/TOFA-9因其粒径、高封装效率和体外药物释放行为而被选为最合适的制剂。Poloxamer 338 浓度为 15%,用于制备原位凝胶制剂。在关节内给药时,将微球分散在含有 15% Poloxamer 338 的原位凝胶中,并对凝胶化温度、粘度、流变学、机械和铺展性进行表征。在对健康细胞进行的细胞培养研究中,MS/TOFA-9 和 PLX-MS/TOFA-9 的安全剂量被确定为 40 µL/mL。在 99mTc 的放射性标记研究中,最佳放射性标记条件被确定为 200 ppm SnCl2 和 0.5 mg 抗坏血酸,99mTc-MS/TOFA-9 和 99mTc-PLX-MS/TOFA-9 均表现出较高的细胞结合能力。总之,尽管还需要进一步的体内实验,但PLX-MS/TOFA-9被认为是一种很有前途的类风湿性关节炎关节内注射剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
期刊最新文献
Targeted therapies for Glioblastoma multiforme (GBM): State-of-the-art and future prospects Knockdown of ENO1 promotes autophagy dependent-ferroptosis and suppresses glycolysis in breast cancer cells via the regulation of CST1. MLLT3 knockdown suppresses proliferation and cell mobility in human lung adenocarcinoma. PARP7i Clinical Candidate RBN-2397 Exerts Antiviral Activity by Modulating Interferon-β Associated Innate Immune Response in Macrophages. Agmatine: An Emerging Approach for Neuroprotection in Recurrent Ischemic Stroke Events in a Murine Model
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1