高浓度环糊精和电解质对蛋白质聚集抑制的协同效应

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Masakazu Fukuda, Kanako Takahashi, Toru Takarada, Shunsuke Saito, Masafumi Tanaka
{"title":"高浓度环糊精和电解质对蛋白质聚集抑制的协同效应","authors":"Masakazu Fukuda, Kanako Takahashi, Toru Takarada, Shunsuke Saito, Masafumi Tanaka","doi":"10.1016/j.xphs.2024.10.004","DOIUrl":null,"url":null,"abstract":"<p><p>The stabilization of protein therapeutics against aggregation is crucial for maintaining their efficacy and safety. This study investigated the synergistic effects of cyclodextrins (CDs) and electrolytes at high concentrations on the stabilization of immunoglobulin G (IgG), insulin, and adeno-associated virus (AAV) vectors. The effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) combined with various electrolytes were evaluated using human plasma-derived IgG as a model protein. The HP-β-CD and L(+)-arginine hydrochloride combination synergistically increased the onset temperature of protein aggregation and inhibited the formation of soluble and insoluble aggregates during long-term storage. Notably, this synergistic effect was not observed when sucrose was used instead of HP-β-CD. Similar synergistic effects were observed with insulin and AAV vectors. The findings suggest that the stabilization mechanism could potentially involve enhanced interactions between HP-β-CD and IgG, preventing protein-protein interactions. However, the combination did not synergistically improve the solubility of free aromatic amino acids, including tyrosine and tryptophan. This study highlights the potential of using the combination of CDs and electrolytes as a promising formulation strategy for stabilizing complex protein therapeutics. Further studies are needed to elucidate the underlying mechanisms and generalize the approach to other proteins with varying physicochemical properties.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition.\",\"authors\":\"Masakazu Fukuda, Kanako Takahashi, Toru Takarada, Shunsuke Saito, Masafumi Tanaka\",\"doi\":\"10.1016/j.xphs.2024.10.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The stabilization of protein therapeutics against aggregation is crucial for maintaining their efficacy and safety. This study investigated the synergistic effects of cyclodextrins (CDs) and electrolytes at high concentrations on the stabilization of immunoglobulin G (IgG), insulin, and adeno-associated virus (AAV) vectors. The effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) combined with various electrolytes were evaluated using human plasma-derived IgG as a model protein. The HP-β-CD and L(+)-arginine hydrochloride combination synergistically increased the onset temperature of protein aggregation and inhibited the formation of soluble and insoluble aggregates during long-term storage. Notably, this synergistic effect was not observed when sucrose was used instead of HP-β-CD. Similar synergistic effects were observed with insulin and AAV vectors. The findings suggest that the stabilization mechanism could potentially involve enhanced interactions between HP-β-CD and IgG, preventing protein-protein interactions. However, the combination did not synergistically improve the solubility of free aromatic amino acids, including tyrosine and tryptophan. This study highlights the potential of using the combination of CDs and electrolytes as a promising formulation strategy for stabilizing complex protein therapeutics. Further studies are needed to elucidate the underlying mechanisms and generalize the approach to other proteins with varying physicochemical properties.</p>\",\"PeriodicalId\":16741,\"journal\":{\"name\":\"Journal of pharmaceutical sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pharmaceutical sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xphs.2024.10.004\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xphs.2024.10.004","RegionNum":3,"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

摘要

稳定蛋白质治疗药物以防止其聚集是保持其疗效和安全性的关键。本研究调查了高浓度环糊精(CD)和电解质对免疫球蛋白 G(IgG)、胰岛素和腺相关病毒(AAV)载体稳定化的协同作用。研究以人血浆衍生 IgG 为模型蛋白,评估了 2-羟丙基-β-环糊精(HP-β-CD)与各种电解质结合的效果。HP-β-CD 和 L(+)- 精氨酸盐酸盐的组合可协同提高蛋白质聚集的起始温度,并抑制长期储存过程中可溶性和不溶性聚集体的形成。值得注意的是,当使用蔗糖代替 HP-β-CD 时,没有观察到这种协同效应。在使用胰岛素和 AAV 载体时也观察到了类似的协同效应。研究结果表明,稳定机制可能是 HP-β-CD 与 IgG 之间的相互作用增强,阻止了蛋白质与蛋白质之间的相互作用。然而,这种组合并不能协同提高游离芳香族氨基酸(包括酪氨酸和色氨酸)的溶解度。这项研究强调了将 CD 与电解质结合使用作为稳定复杂蛋白质疗法的制剂策略的潜力。不过,还需要进一步的研究来阐明其基本机制,并将这种方法推广到具有不同理化性质的其他蛋白质中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synergistic effect of cyclodextrins and electrolytes at high concentrations on protein aggregation inhibition.

The stabilization of protein therapeutics against aggregation is crucial for maintaining their efficacy and safety. This study investigated the synergistic effects of cyclodextrins (CDs) and electrolytes at high concentrations on the stabilization of immunoglobulin G (IgG), insulin, and adeno-associated virus (AAV) vectors. The effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) combined with various electrolytes were evaluated using human plasma-derived IgG as a model protein. The HP-β-CD and L(+)-arginine hydrochloride combination synergistically increased the onset temperature of protein aggregation and inhibited the formation of soluble and insoluble aggregates during long-term storage. Notably, this synergistic effect was not observed when sucrose was used instead of HP-β-CD. Similar synergistic effects were observed with insulin and AAV vectors. The findings suggest that the stabilization mechanism could potentially involve enhanced interactions between HP-β-CD and IgG, preventing protein-protein interactions. However, the combination did not synergistically improve the solubility of free aromatic amino acids, including tyrosine and tryptophan. This study highlights the potential of using the combination of CDs and electrolytes as a promising formulation strategy for stabilizing complex protein therapeutics. Further studies are needed to elucidate the underlying mechanisms and generalize the approach to other proteins with varying physicochemical properties.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信