Journal
JOURNAL OF CONTROLLED RELEASE
Volume 329, Issue -, Pages 1117-1128Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2020.10.039
Keywords
Organophosphorus poisoning; Blood-brain barrier; Obidoxime; Aptamer; Liposomes; Brain-targeted delivery
Funding
- Military Medical Scientific and Technological Project [AWS15J007, BWS16J007, AWS17J007]
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The study developed transferrin receptor aptamer-functionalized liposomes (Apt-LP) to deliver AChE reactivator across the blood-brain barrier, showing promising results in treating organophosphorus poisoning by improving drug transport efficiency to the brain.
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.
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