Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals

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	Design and preparation of chimeric hyaluronidase as a chaperone for the subcutaneous administration of biopharmaceuticals
	Liu, Shan 1,2; Xie, Bo 1; Wei, Wei 1; Hui, Mizhou 1; Su, Zhiguo 1,3
刊名	BIOCHEMICAL ENGINEERING JOURNAL
	2016-08-15
卷号	112 期号:AUG 页码:32-41
关键词	Recombinant DNA Fed-batch culture Purification Biomedical Long-acting hyaluronidase Subcutaneous administration
ISSN号	1369-703X
英文摘要	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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine ; Technology
类目[WOS]	Biotechnology & Applied Microbiology ; Engineering, Chemical
研究领域[WOS]	Biotechnology & Applied Microbiology ; Engineering
关键词[WOS]	RECOMBINANT HUMAN HYALURONIDASE ; PROTEINS ; TRANSPORT ; CELLS ; HOST
收录类别	SCI
语种	英语
WOS记录号	WOS:000377731700004
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/21148]
专题	过程工程研究所_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.