In vitro evaluation of two different types of obidoxime-loaded nanoparticles for cytotoxicity and blood-brain barrier transport

Nerve agents (NA) are chemical warfare munitions and their exposure causes a progressive inhibition of acetylcholinesterase (AChE). This inhibition causes NA-induced brain damage in central nervous system (CNS). Oximes reactivate AChE in both the peripheral nervous system and the CNS. Transport of the oxime across the blood-brain barrier (BBB) in the existed therapeutic concentrations at the brain parenchyma determines the effectiveness of antidote therapy on respiratory depression and NA-induced brain damage. However, oximes could not cross the BBB in therapeutic concentrations. The aim of this study was to load AChE reactivator obidoxime chloride to PLGA and PEG-b-PLGA nanoparticles and to improve the BBB transport of the molecule. Brain microvascular endothelial cells were used as the BBB model. 79.3 ± 4.2% of obidoxime was released from PLGA nanoparticles and 88.2 ± 4.4% of obidoxime was released from PEG-b-PLGA nanoparticles within 24 h. It was found that PEG-b-PLGA nanoparticles were ideal drug carrier because of its low tissue toxicity, few side effects, and controllable drug release profile. Transport efficiency of obidoxime across the BBB is a major challenge in the prevention of the CNS, the effectiveness of NA poisoning and new strategies like using obidoxime-loaded PEG-b-PLGA nanoparticles could overcome this challenge for the management of NA-induced brain damage.