کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1423584 | 1509019 | 2016 | 6 صفحه PDF | دانلود رایگان |
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 ~ 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.
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Journal: Journal of Controlled Release - Volume 230, 28 May 2016, Pages 73–78