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Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight
Zhai, Yanqin1,2; Zhao, Yongjiang1,2; Lei, Jiandu1; Su, Zhiguo1; Ma, Guanghui1; Lei, JD
2009-07-15
Source PublicationJOURNAL OF BIOTECHNOLOGY
ISSN0168-1656
Volume142Issue:3-4Pages:259-266
AbstractRecombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, I he high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxypoly(ethylene glycol)-propionaldehyde (niPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity. separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and rnono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy. (C) 2009 Elsevier B.V. All rights reserved.
KeywordDrug Bioavailability Granulocyte Colony Stimulating Factor (G-csf) Serum Half-life Site-specific Pegylation
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1016/j.jbiotec.2009.05.012
Indexed BySCI
Language英语
WOS KeywordCOLONY-STIMULATING FACTOR ; ION-EXCHANGE CHROMATOGRAPHY ; ACUTE MYELOID-LEUKEMIA ; POLY(ETHYLENE GLYCOL) ; CLINICAL-APPLICATIONS ; INTERFERON ALPHA-2A ; DAILY FILGRASTIM ; PEGFILGRASTIM ; CHEMOTHERAPY ; PROTEINS
WOS Research AreaBiotechnology & Applied Microbiology
WOS SubjectBiotechnology & Applied Microbiology
WOS IDWOS:000268823400011
Citation statistics
Cited Times:46[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/6634
Collection生化工程国家重点实验室
Corresponding AuthorLei, JD
Affiliation1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Zhai, Yanqin,Zhao, Yongjiang,Lei, Jiandu,et al. Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight[J]. JOURNAL OF BIOTECHNOLOGY,2009,142(3-4):259-266.
APA Zhai, Yanqin,Zhao, Yongjiang,Lei, Jiandu,Su, Zhiguo,Ma, Guanghui,&Lei, JD.(2009).Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight.JOURNAL OF BIOTECHNOLOGY,142(3-4),259-266.
MLA Zhai, Yanqin,et al."Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight".JOURNAL OF BIOTECHNOLOGY 142.3-4(2009):259-266.
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