کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5433849 1509001 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Precise and combinatorial PEGylation generates a low-immunogenic and stable form of human growth hormone
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Precise and combinatorial PEGylation generates a low-immunogenic and stable form of human growth hormone
چکیده انگلیسی

In this study, we aimed to develop a safe and stable form of human growth hormone (hGH) and to refine PEGylation methods for therapeutic proteins via genetic code expansion. Through this precise approach, a series of polyethylene glycol (PEG) moieties and sites were combined in various ways. Additionally, the effects of combinatorial PEGylation on the biological, pharmacological, and immunogenic properties of hGH in vitro and vivo were analyzed. Our results showed that combinatorial PEGylation at Y35, G131, and K145 significantly reduced immunogenicity and improved pharmacokinetic (PK) profiles compared with mono-PEGylation, while retaining biological activity. Upon re-examination of the pharmacodynamics in hypophysectomized rats, multi-PEGylated hGH was found to be much more stable than mono-PEGylated hGH. Thus, this method for combinatorial, precise PEGylation may facilitate the development of next-generation, long-acting hGH with low immunogenicity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 249, 10 March 2017, Pages 84-93
نویسندگان
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