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Journal of Nanoparticle Research

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01-11-2020 | Research paper

c(RGDyK)-mediated Pluronic-PBCA nanoparticles through the blood-brain barrier to enhance the treatment of central organophosphorus intoxication

Authors: Yuan Liu, Xiaoli Zhou, Xiaofeng Wang, Qian Li, Dongfeng Yin

Published in: Journal of Nanoparticle Research | Issue 11/2020

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Abstract

Human usually uses oximes as acetylcholinesterase (AChE)-activated antidotes to treat organophosphorus (OP) compound poisoning. In addition, drugs such as atropine can also be used for its detoxification treatment. However, the natural blood-brain barrier (BBB) severely limits the penetration of these drugs into the central nervous system. As a widely used reactivator, HI-6 is difficult to penetrate the BBB due to its hydrophilicity. Therefore, we hope that a large amount of HI-6 can penetrate the BBB through the drug delivery system. They can quickly release and activate the inhibited AChE in the center. Polybutylcyanoacrylate (PBCA) has good biodegradability and biocompatibility, which ensures the safety of the treatment. Pluronic P85 gets the advantages of inhibiting P-glycoprotein (P-gp) efflux and improving drug solubility. In this study, the HI-6-loaded nanoparticles that conjugated with c(RGDyK) cyclic peptide were successfully synthesized, with encapsulation efficiency 63.69%, drug loading 6.2%, average particle size 166.9 nm, and zeta potential − 22.0 mV. The shape was round and evenly distributed. The BBB model was established by astrocytes and brain capillary endothelial cells, and the transendothelial cell resistance values of the BBB model could reach 183 Ω. The penetration effect of the c(RGDyK)-modified nanoparticles was about 4 times the free HI-6 on the BBB model in vitro. The c(RGDyK)-modified nanoparticles were more effective at targeting the brain than the unmodified nanoparticles in vivo. In addition, reactivation evaluation showed that the modified nanoparticles had a higher reactivation rate for poisoned mice, indicating that the nanoparticles modified with c(RGDyK) cyclic peptide had more central targeting. The successful implementation of this study is expected to improve the treatment level of nerve agents.

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Title: c(RGDyK)-mediated Pluronic-PBCA nanoparticles through the blood-brain barrier to enhance the treatment of central organophosphorus intoxication
Authors: Yuan Liu
Xiaoli Zhou
Xiaofeng Wang
Qian Li
Dongfeng Yin
Publication date: 01-11-2020
Publisher: Springer Netherlands
Published in: Journal of Nanoparticle Research / Issue 11/2020
Print ISSN: 1388-0764
Electronic ISSN: 1572-896X
DOI: https://doi.org/10.1007/s11051-020-05039-7

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