albumin - publications

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1. Biol Pharm Bull. 2012;35(3):280-8.

Site-Specific Chemical Modification of Human Serum Albumin with Polyethylene
Glycol Prolongs Half-life and Improves Intravascular Retention in Mice.

Zhao T, Cheng YN, Tan HN, Liu JF, Xu HL, Pang GL, Wang FS.

Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical
Sciences, Shandong University.

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‚ÄČkDa) 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.

PMID: 22382312 [PubMed - in process]