Butyrylcholinesterase nanocapsule as a long circulating bioscavenger with reduced immune response

JOURNAL OF CONTROLLED RELEASE

卷:230

Article

Zhang, Peng¹  Jain, Priyesh¹  Tsao, Caroline¹  Sinclair, Andrew¹  Sun, Fang¹  Hung, Hsiang-Chieh¹  Bai, Tao¹  Wu, Kan¹  Jiang, Shaoyi¹ 

[1] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA

关键词: Nanogel;    Butyrylcholinesterase;    Organophosphate;    Circulation;    Protein delivery;    Immune response;   

DOI  :  10.1016/j.jconrel.2016.04.008

来源: Elsevier

【 摘 要 】

Butyrylcholinesterase (BChE) is the most promising bioscavenger candidate to treat or prevent organophosphate (OP) poisoning. However, the clinical application of BChE is limited by two obstacles: an inadequate circulation half-life and limited sources for production. Although several modification technologies including glycosylation and PEGylation have been developed to improve its pharmacokinetics, none of them have been able to outperform blood-derived native BChE. In this work, we designed a long-circulating bioscavenger nanogel by coating equine serum-derived BChE with a zwitterionic polymer gel layer. This zwitterionic gel coating protected BChE from denaturation and degradation under harsh conditions. Notably, the nanocapsule exhibited a long circulation half-life of similar to 45 h, a three-fold increase from the unmodified native version, enabling both therapeutic and prophylactic applications. In addition, the gel coating reduced the immunogenicity of equine BChE, unlocking the possibility to use non-human derived BChE as an OP bioscavenger in humans. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

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