Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The asprepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), ζpotential, Brunauer−Emmett−Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents.

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.

A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N , N -dimethylammonium cations in the pores of the anionic, biocompatible metal–organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10–50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs.