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Pharmaceutical development and technology, v.11 no.4, 2006년, pp.513 - 519
Hee Na, Dong (College of Pharmacy, Kyungsung University, Nam-ku, Busan, Korea) , Seok Youn, Yu (Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, Jangan-ku, Suwon, Korea) , Bok Lee, In (Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, Jangan-ku, Suwon, Korea) , Ji Park, Eun (Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, Jangan-ku, Suwon, Korea) , Jeon Park, Chong (Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, Jangan-ku, Suwon, Korea) , Choon Lee, Kang (Drug Targeting Laboratory, College of Pharmacy, SungKyunKwan University, Jangan-ku, Suwon, Korea)
The purpose of this study was to investigate the effect of size of polyethylene glycol (PEG) conjugated to recombinant human epidermal growth factor (rhEGF) on its stability in skin wound tissue and in vitro biological activity to find the desirable conjugate as topical therapeutic agent for wound healing. Site-specific PEGylation at N-terminus of rhEGF was performed with monomethoxy PEG-Butyraldehyde derivatives (MW 2, 5, and 20 kDa). Mono-PEG-rhEGFs retained 60–70% of biological activity of native rhEGF, and the effect of PEG size was not significant. The improvement of stability in the rat skin wound tissue was dependent on the increase of the PEG size attached. The degradation half-lives of native rhEGF, mono-PEG-2K-, −5K-, and −20K-rhEGFs were 1.1, 3.1, 5.2, and 41.5 hr, respectively. Therefore, mono-PEG-20K-rhEGF was considered to be the most desirable in terms of the increase of stability and the preservation of biological activity. This study suggests that the high molecular weight PEG at N-terminus of rhEGF would give a satisfactory stabilizing effect and thus may improve therapeutic efficacy in clinical use.
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