Reactivation of nanoparticulated HI-6 on acetylcholinesterase activity in soman poisoned mice
10.3867/j.issn.1000-3002.2014.02.019
- VernacularTitle:纳米化酰胺磷定对梭曼中毒小鼠乙酰胆碱酯酶的重活化作用
- Author:
Feijian WANG
;
Jun YANG
;
Feng CHENG
;
Wanhua LI
;
Zhiyong NIE
;
Yuan LUO
;
Xin SUI
;
Zhao WEI
;
Zhibing ZHENG
;
Yongan WANG
;
Tongyu FANG
- Publication Type:Journal Article
- Keywords:
nerve agents;
acetylcholinesterase;
nano-reactivator;
HI-6;
reactivation
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(2):255-261
- CountryChina
- Language:Chinese
-
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.
