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

Autor: Zhang Y; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China., He J; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China., Shen L; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China., Wang T; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China., Yang J; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China., Li Y; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China., Wang Y; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China. Electronic address: yonganw@126.com., Quan D; Academy of Military Medical Science, Institutes of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Counter Measures, Beijing 100850, China. Electronic address: qdqwzb@163.com.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2021 Jan 10; Vol. 329, pp. 1117-1128. Date of Electronic Publication: 2020 Oct 21.
DOI: 10.1016/j.jconrel.2020.10.039
Abstrakt: 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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: