Site-Specific Chemical Modification of Human Serum Albumin with Polyethylene Glycol Prolongs Half-life and Improves Intravascular Retention in Mice
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- Zhao Ting
- Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University
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- Cheng Yan-Na
- Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University
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- Tan Hai-Ning
- National Glycoengineering Research Center, Shandong University
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- Liu Jin-Feng
- Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University
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- Xu Huan-Li
- Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University
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- Pang Guang-Li
- Shandong Taibang Biological Products Co., Ltd.
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- Wang Feng-Shan
- Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University National Glycoengineering Research Center, Shandong University
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Human serum albumin (HSA) is used as an important plasma volume expander in clinical practice. However, the infused HSA may extravasate into the interstitial space and induce peripheral edema in treating the critical illness related to marked increase in capillary permeability. Such poor intravascular retention also demands a frequent administration of HSA. We hypothesize that increasing the molecular weight of HSA by PEGylation may be a potential approach to decrease capillary permeability of HSA. In the present study, HSA was PEGylated in a site-specific manner and the PEGylated HSA carrying one chain of polyethylene glycol (PEG) (20 kDa) per HSA molecule was obtained. The purity, PEGylated site and secondary structure of the modified protein were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), thiol group blockage method and circular dichroism (CD) measurement, respectively. In addition, the pharmacokinetics in normal mice was investigated, vascular permeability of the PEGylated HSA was evaluated in lipopolysaccharide (LPS)-induced lung injury mouse model and the pharmacodynamics was investigated in LPS-induced sepsis model with systemic capillary leakage. The results showed that the biological half-life of the modified HSA was approximately 2.3 times of that of the native HSA, PEG-HSA had a lower vascular permeability and better recovery in blood pressure and haemodilution was observed in rats treated with PEG-HSA. From the results it can be inferred that the chemically well-defined and molecularly homogeneous PEGylated HSA is superior to HSA in treating capillary permeability increase related illness because of its longer biological half-life and lower vascular permeability.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 35 (3), 280-288, 2012
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204631562496
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- NII論文ID
- 130001872307
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC383nvVWhsw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 023439532
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- PubMed
- 22382312
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可