CAS OpenIR  > 生化工程国家重点实验室
Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals
Liu, Shan1,2; Xie, Bo1; Wei, Wei1; Hui, Mizhou1; Su, Zhiguo1,3
2016-08-15
发表期刊BIOCHEMICAL ENGINEERING JOURNAL
ISSN1369-703X
卷号112期号:AUG页码:32-41
摘要Subcutaneous (SC) delivery of biomacromolecular pharmaceuticals such as proteins often encounter barriers in the extracellular matrix, especially the hyaluronan (HA) network. In this study, chimeric hyaluronidases were designed, prepared and tested for assisting biopharmaceuticals in ID administration in mice as replacement of SC administration. The chimeras were hyaluronidase (rhPH20) conjugated with human serum albumin (rhPH20-HSA) and antibody Fc fragment (rhPH20-Fc). Expression of the new protein was undertaken in CHO cells cultured in a 5-L disposable bioreactor. Purification was carried out by a series of chromatographic methods to obtain high-purity products of 61 kDa (rhPH20), 79 kDa (rhPH20-HSA) and 190 kDa (rhPH20-Fc). The chimeric proteins rhPH20-HSA and rhPH20-Fc performed fairly well as spreading factors in short-term trypan blue intradermal (ID) infusion in comparison with recombinant hyaluronidase (rhPH20). They extended the channel opening from 24h (rhPH20) to 85-120h in vivo. The specific activity of rhPH20-Fc was 35,600 U/mg, higher than that of rhPH20-HSA (10,000 U/mg). Co-administration of rhPH20-Fc with two biomacromolecular pharmaceuticals, Stelara (150 KDa) and TNFRII-Fc-IL1ra (TFI, 250 kDa), through an ID route increased the bioavailability from 86% to 93% and from 64% and 97%, respectively, compared with rhPH20. The pharmacokinetic profile of ID administrated larger TFI was significantly improved through cooperation with the long-acting hyaluronidase. (c) 2016 Elsevier B.V. All rights reserved.
关键词Recombinant Dna Fed-batch Culture Purification Biomedical Long-acting Hyaluronidase Subcutaneous Administration
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine ; Technology
DOI10.1016/j.bej.2016.03.013
收录类别SCI
语种英语
关键词[WOS]RECOMBINANT HUMAN HYALURONIDASE ; PROTEINS ; TRANSPORT ; CELLS ; HOST
WOS研究方向Biotechnology & Applied Microbiology ; Engineering
WOS类目Biotechnology & Applied Microbiology ; Engineering, Chemical
项目资助者National High Technology Research and Development Program of China(2012AA021202) ; National Key Basic Research Program of China(2013CB733600)
WOS记录号WOS:000377731700004
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/21148
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Nanjing 210009, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714
Liu, Shan,Xie, Bo,Wei, Wei,et al. Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals[J]. BIOCHEMICAL ENGINEERING JOURNAL,2016,112(AUG):32-41.
APA Liu, Shan,Xie, Bo,Wei, Wei,Hui, Mizhou,&Su, Zhiguo.(2016).Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals.BIOCHEMICAL ENGINEERING JOURNAL,112(AUG),32-41.
MLA Liu, Shan,et al."Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals".BIOCHEMICAL ENGINEERING JOURNAL 112.AUG(2016):32-41.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
Design and preparati(2142KB)期刊论文出版稿开放获取CC BY-NC-SA浏览 请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Liu, Shan]的文章
[Xie, Bo]的文章
[Wei, Wei]的文章
百度学术
百度学术中相似的文章
[Liu, Shan]的文章
[Xie, Bo]的文章
[Wei, Wei]的文章
必应学术
必应学术中相似的文章
[Liu, Shan]的文章
[Xie, Bo]的文章
[Wei, Wei]的文章
相关权益政策
暂无数据
收藏/分享
文件名: Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。