Brain-targeted delivery of obidoxime, using aptamer-modified liposomes, for detoxification of organophosphorus compounds

被引：41

作者：

Zhang, Yadan ^{[1
,2
]}

He, Junlin ^{[1
,2
]}

Shen, Liao ^{[1
,2
]}

Wang, Tao ^{[1
,2
]}

Yang, Jun ^{[1
,2
]}

Li, Yao ^{[1
,2
]}

Wang, Yongan ^{[1
,2
]}

Quan, Dongqin ^{[1
,2
]}

机构：

[1] Acad Mil Med Sci, Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China

[2] State Key Lab Toxicol & Med Counter Measures, Beijing 100850, Peoples R China

来源：

JOURNAL OF CONTROLLED RELEASE | 2021年 / 329卷

关键词：

Organophosphorus poisoning; Blood-brain barrier; Obidoxime; Aptamer; Liposomes; Brain-targeted delivery; BARRIER PENETRATION; OXIME; THERAPEUTICS; EFFICACY; HI-6;

D O I：

10.1016/j.jconrel.2020.10.039

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity.

引用

页码：1117 / 1128

页数：12

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