ABSTRACT
OBJECTIVE Based on different drug loading models,three types of nanoparticulated HI-6 were prepared and their reactivations on inhibited acetylcholinesterase (AChE)in peripheral and central nervous syste ms were evaluated and compared in so man-intoxicated mice.METHODS Three kinds of nano-reactivators including HI-6 loaded human serum albunin nanoparticle (HSA-HI-6 NP),HI-6 absorptive mesoporous silica nanoparticle(MSN-HI-6),polylactico-glycolic acid nanoparticle coated HI-6 (PLGA-HI-6 NP)were prepared.The characteristic of all blank nanocarriers was observed through elec-tron microscope.HI-6 release rate of nano-reactivators was also determined in vitro.Then the reactiva-tion rate of nano-reactivators at a constant HI-6 dosage(22 mg·kg -1 )on so man-inhabited AChE both in blood and brain was assessed the so man intoxicated mice(120 μg·kg -1 ,sc).RESULTS All the syn-thetic nanocarriers met the de mand for nanodrug use in vivo.The rate of HI-6 release of nano-reactiva-tors was HI-6 >HSA-HI-6 NPs >MSN-HI-6 >PLGA-HI-6 NP in vitro.On the reactivations of so man-inhibited mice blood AChE,the free HI-6 and HSA-HI-6 NPs,as well as MSN-HI-6 showed co mparable reactivation rates(20% -30%)but were greater than that of PLGA-HI-6 NPs (6.2%)(P <0.01 ). However on the reactivations of so man-inhibited mice brain AChE,the reactivation rate of HSA-HI-6 NP (15.3%)was significantly higher than that of PLGA-HI-6 NP(3.3%)and free HI-6(6.3)(P<0.01 ).In addition,MSN-HI-6 group had a significant reactivation rate compared to PLGA-HI-6 NPs(P <0.01 ). But there was no statistic difference between MSN-HI-6 and free HI-6.CONCLUSION The reactivation potency changed obviously with different drug loading models and HSA-HI-6 NPs had the most potent reactivation on so man-inhibited AChE in both blood and brain.
ABSTRACT
Organophosphate pesticides are used extensively worldwide, and poisoning by these agents, particularly in developing nations is a public health problem. Organophosphorous nerve agents are still considered as potential threat in both military or terrorism situations. The mechanism of toxicity is the inhibition of acetylcholinesterase, resulting in accumulation of the neurotransmitter acetylcholine and continued stimulation of acetylcholine receptors both in central and peripheral nervous systems. Beside acute cholinergic crisis, organophosphates are capable of producing several subacute or chronic neurological syndromes. The well described intermediate syndrome (IMS) emerges 1-4 days after an apparently well treated cholinergic crisis. The standard treatment consists of reactivation of inhibited acetylcholinesterase with an oxime antidote (pralidoxime, obidoxime, HI-6 and Hlo7) and reversal of the biochemical effects of acetylcholine with atropine. The newer oximes HI-6 and Hlo& are much more suitable and efficacious acetylcholinesterase reactivator for severe acute nerve agent induced poisoning than currently used pralidoxime or obidoxime. Patients who receive treatment promptly usually recover from acute toxicity but may suffer from neurologic sequelae.