N-terminal PEGylation of human serum albumin and investigation of its pharmacokinetics and pulmonary microvascular retention
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Human serum albumin (HSA) is used as an important plasma volume expander in clinical practice. In the present study, HSA was N-terminally PEGylated and a PEGylated HSA (PEG-HSA) carrying one chain of PEG (20 kDa) per HSA molecule was obtained. The purity, secondary structure and hydrodynamic radius of the modified protein were characterized using sodium dodecyl sulfate polyacrylamide gel electrophoresis, circular dichroism measurements, and dynamic light scattering, respectively. The pharmacokinetics in normal mice and vascular permeability of the PEG-HSA in a lipopolysaccharide-induced acute lung injury mice model were evaluated. The results showed that the biological half-life of the modified HSA was approximately 2.2 times of that of native HSA, and PEG-HSA had a lower vascular permeability which suggested that PEGylation of HSA could reduce extravasation into interstitial space. It can be inferred that due to the prolonged half-life time and enhanced vascular retention, the molecularly homogeneous PEG-HSA may be a superior candidate as a plasma volume expander in treating capillary permeability increase related illness.
- 特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会の論文
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会 | 論文
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