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http://dx.doi.org/10.4333/KPS.2010.40.6.379

Long-acting Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) with a Trimer-Structured Polyethylene Glycol  

Jo, Yeong-Woo (Biopharmaceutical Research Laboratory, Dong-A Pharm. Co. Ltd.)
Lee, Mee-Yong (Biopharmaceutical Research Laboratory, Dong-A Pharm. Co. Ltd.)
Choi, Yun-Kyu (Biopharmaceutical Research Laboratory, Dong-A Pharm. Co. Ltd.)
Lee, Sung-Hee (Biopharmaceutical Research Laboratory, Dong-A Pharm. Co. Ltd.)
Kang, Soo-Hyoung (Biopharmaceutical Research Laboratory, Dong-A Pharm. Co. Ltd.)
Na, Kun (Department of Biotechnology, The Catholic University of Korea)
Youn, Yu-Seok (College of Pharmacy, Pusan National University)
Choi, Eung-Chil (College of Pharmacy, Seoul National University)
Publication Information
Journal of Pharmaceutical Investigation / v.40, no.6, 2010 , pp. 379-386 More about this Journal
Abstract
Mono PEGylated rhG-CSF (PEG-G-CSF) prepared by utilizing unique PEG was purified and characterized by cation-exchange chromatography. A unique, trimer-structured PEG was chosen for PEGylation of rhG-CSF among various PEG moieties. The in-vitro bioactivity, stability, and pharmacokinetics of mono-PEG-G-CSF were examined and compared to those of native rhG-CSF. Mono PEG-G-CSF exhibited reduced in-vitro bioactivity to native rhG-CSF but showed an excellent in-vivo bioactivity and stability. Furthermore, it showed markedly reduced clearance in rats, thereby increasing the biological half-life by about 4.5-fold compared to that of native rhG-CSF. The results suggest that this unique, trimer-structured 23 kDa PEG can provide advantages to improve the bioactivity of therapeutic proteins in clinical use.
Keywords
G-CSF; PEG; Structure; Characteristics;
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