Nanoparticle-Delivered 2-PAM for Rat Brain Protection against Paraoxon Central Toxicity

Abstract

Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime chloride (2-PAM), in SLNs appears to be a suitable strategy for protection against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2-PAM-loaded SLNs were developed for brain targeting and delivery via intravenous (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency (∼90%) and loading capacity (maximum 30.8 ± 1%). Drug-loaded particles had a mean hydrodynamic diameter close to 100 nm and high negative zeta potential (-54 to -15 mV). These properties contribute to improve long-term stability of 2-PAM-SLNs when stored both at room temperature (22 °C) and at 4 °C, as well as to longer circulation time in the bloodstream compared to free 2-PAM. Paraoxon-poisoned rats (2 × LD) were treated with 2-PAM-loaded SLNs at a dose of 2-PAM of 5 mg/kg. 2-PAM-SLNs reactivated 15% of brain AChE activity. Our results confirm the potential use of SLNs loaded with positively charged oximes as a medical countermeasure both for protection against OPs poisoning and for postexposure treatment.

Nanometric MIL-125-NH2 Metal–Organic Framework as a Potential Nerve Agent Antidote Carrier

“…The discrepancy between experimental measurements and theoretical loading might be mainly related to the use of generic force fields (UFF in particular), not specifically developed for such precise applications, as well as the presence of the impregnation solvent (i.e., methanol), which competes with 2-PAM for adsorption within the MIL-125-NH 2 pores. Although the 2-PAM loading capacity of MIL-125-NH 2 is lower than in solid lipid nanoparticles (SLN; 30.8% w / w ) and poly(lactic-co-glycolic acid) nanoparticles (PLGA; 7.1–68.8% w / w ), the loading rate is in the same range than the previously reported liposome system (5.3–11.9% w / w ) [ 16 , 17 , 18 ]. Nevertheless, the photocatalytic activity of MIL-125-NH 2 could be an important advantage in simultaneously degrading nerve agents.…”

“…Particularly, incorporation of 2-PAM into different nanocarriers has been proposed to overcome the previously mentioned drawback [ 15 , 16 , 17 ]. Although mesoporous silica and solid lipid NPs have shown promising results, the problem is far from being solved [ 18 ]. Apart from the potential delivery of 2-PAM into the brain, sustained release of 2-PAM into the bloodstream could lead to pharmaceutically relevant blood levels of the drug for prolonged periods of time, which would be beneficial in case of intoxication by more persistent agents such as VX (ethyl({2-[bis(propan-2-yl)amino]ethyl}sulfanyl)(methyl)phosphinate) [ 19 ].…”

Sucupira Oil-Loaded Nanostructured Lipid Carriers (NLC): Lipid Screening, Factorial Design, Release Profile, and Cytotoxicity

“…To overcome the above-mentioned issues and to benefit from their biological activities, nanoparticles have been proposed to load EOs for therapeutic use [7,9,30]. Nanoparticles have the advantages of site-specific targeted delivery of bioactive molecules, improving their bioavailability with minimal toxicological events [29,31]. Among different types of nanoparticles, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have a special interest due to their lipid composition and solid matrix [32].…”

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

“…cm -1 in 0.0025 M phosphate buffer at pH = 7.4) The parameters were calculated against appropriate calibration curve, using the following equation[34]:…”