A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences , 8 Arbuzov Street, Kazan 420088, Russia.
Kazan Federal University , 18 Kremlyovskaya Street, Kazan 420008, Russia.
ACS Appl Mater Interfaces. 2017 May 24;9(20):16922-16932. doi: 10.1021/acsami.7b04163. Epub 2017 May 15.
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.
固体脂质纳米粒（SLNs）是最有前途的纳米载体之一，可用于靶向血脑屏障（BBB），将药物递送到中枢神经系统（CNS）。将乙酰胆碱酯酶重激活剂，氯化羟肟酸（2-PAM）包封在 SLNs 中，似乎是一种防止有机磷剂（OPs）中毒和暴露后治疗的合适策略。开发了载有 2-PAM 的 SLNs 用于通过静脉内（iv）给药进行脑靶向和递药。2-PAM-SLNs 显示出高的 2-PAM 包封效率（约 90%）和载药量（最大 30.8 ± 1%）。载药颗粒的平均水动力直径接近 100nm，具有高的负 zeta 电位（-54 至-15mV）。这些特性有助于改善 2-PAM-SLNs 在室温（22°C）和 4°C 下储存时的长期稳定性，以及与游离 2-PAM 相比在血液中更长的循环时间。用 2-PAM 剂量为 5mg/kg 的载有 2-PAM 的 SLNs 治疗对氧磷中毒的大鼠（2×LD）。2-PAM-SLNs 使 15%的脑 AChE 活性得到恢复。我们的结果证实了负载正电荷肟的 SLNs 作为一种医疗对策，无论是用于防止 OPs 中毒还是用于暴露后治疗，都具有潜在的用途。
