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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
AbstractSubcutaneous (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.
KeywordRecombinant Dna Fed-batch Culture Purification Biomedical Long-acting Hyaluronidase Subcutaneous Administration
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Technology
Indexed BySCI
WOS Research AreaBiotechnology & Applied Microbiology ; Engineering
WOS SubjectBiotechnology & Applied Microbiology ; Engineering, Chemical
Funding OrganizationNational High Technology Research and Development Program of China(2012AA021202) ; National Key Basic Research Program of China(2013CB733600)
WOS IDWOS:000377731700004
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Document Type期刊论文
Affiliation1.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
Recommended Citation
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.
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