PUBLICATION
Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe)
- Authors
- Zhao, D., Liu, J., Zhou, Y., Zhang, L., Zhong, Y., Yang, Y., Zhao, B., Yang, M., Wang, Y.
- ID
- ZDB-PUB-230304-34
- Date
- 2023
- Source
- ACS applied materials & interfaces 15(10): 12631-12642 (Journal)
- Registered Authors
- Zhao, Baoquan
- Keywords
- drug delivery, metal−organic framework, nerve agent, pralidoxime chloride, preparation and characterization, targeted treatment
- MeSH Terms
-
- Acetylcholinesterase/metabolism
- Animals
- Blood-Brain Barrier/metabolism
- Cholinesterase Inhibitors
- Cholinesterase Reactivators*
- Iron
- Mice
- Nerve Agents*
- Oximes
- Poisoning*
- Zebrafish/metabolism
- PubMed
- 36867458 Full text @ ACS Appl. Mater. Interfaces
Citation
Zhao, D., Liu, J., Zhou, Y., Zhang, L., Zhong, Y., Yang, Y., Zhao, B., Yang, M., Wang, Y. (2023) Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe). ACS applied materials & interfaces. 15(10):12631-12642.
Abstract
It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping