Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents

Abstract

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.

Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals

“…The temperature range of decomposition of 2-PAM is basically comparable with the data reported in the literature. 37,38 In the fourth and final stage (>400 °C), the bio-MOF-1 framework decomposed, which is consistent with previous reports. 19 From the TGA analysis result together with the elemental analysis result, it was determined that the loaded 2-PAM accounted for 21.7 wt % of the 2-PAM@bio-MOF-1.…”

Penetrating the Blood–Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe)

“…To achieve sustained and stable blood drug concentrations and to overcome the blood−brain barrier, drug-loading materials are considered the best solution. Thus, liposomes, 24−27 PLGA, 28 and metal organic frameworks (MOFs) 29,30 have been loaded with 2-PAM, and only a few in vivo tests have been reported. [24][25][26][27]29 Although these works have shown promising results, the problem has not yet been solved, and the development of nanoformulations of 2-PAM and their application for protection of the central nervous system is still in its infancy.…”

“…To achieve sustained and stable blood drug concentrations and to overcome the blood–brain barrier, drug-loading materials are considered the best solution. Thus, liposomes, − PLGA, and metal organic frameworks (MOFs) , have been loaded with 2-PAM, and only a few in vivo tests have been reported. − , Although these works have shown promising results, the problem has not yet been solved, and the development of nanoformulations of 2-PAM and their application for protection of the central nervous system is still in its infancy. Among the various types of drug carriers reported, MOFs are considered to be a very promising class of drug carriers − with advantages, such as easy surface functionalization, high drug loading capacity, controllable drug release in biological environments, controllable synthetic particle size, and adjustable pore size .…”

Oxime@Zirconium-Metal–Organic Framework Hybrid Material as a Potential Antidote for Organophosphate Poisoning

“…Oximes exert a nucleophilic attack on the P atom of the enzyme–OP adduct, resulting in removal of the phosphoryl moiety from the enzyme active site and the eventual AChE reactivation . However, while low oxime concentrations lead to inefficient reactivation rates, large amounts of reactivator have been shown to cause inhibition of the enzyme. , Thus, oxime dosage is a key parameter during OP-poisoning detoxification. In this sense, the current treatment entails the intravenous administration of a small reactivator dose for multiple times.…”

“…In this sense, the current treatment entails the intravenous administration of a small reactivator dose for multiple times. However, this method generates significant fluctuations in the oxime concentration in the blood, resulting in a poor therapeutic performance . Therefore, novel systems ensuring a controlled and sustained oxime concentration in the body are highly targeted .…”