title: N-terminal PEGylation of human serum albumin and investigation of its pharmacokinetics and pulmonary microvascular retention.
abstract: 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 HAS (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.
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Ji'nan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Aizhen
authors.initials: A
authors.lastname: Zong
authors.forename: Haining
authors.initials: H
authors.lastname: Tan
authors.forename: Xinlei
authors.initials: X
authors.lastname: Song
authors.forename: Shuo
authors.initials: S
authors.lastname: Meng
authors.forename: Chunxia
authors.initials: C
authors.lastname: Song
authors.forename: Guangli
authors.initials: G
authors.lastname: Pang
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002942:Circular Dichroism; D006801:Humans; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D012709:Serum Albumin; D011092:Polyethylene Glycols