Organophosphorus agents, also known as nerve agents, are very dangerous chemicals that were used as chemical warfare agents. HI-6 is one of the most promising reactivators which is effective in reactivating AChE inhibited by many nerve agents. However, the fast in-vivo clearance of HI-6 became a large barrier for first aid use under some sophisticated circumstances. In this study, PEGylated liposomes loading HI-6 were prepared and evaluated in vitro and in vivo. For PEG-LP-HI-6, the optimal formulation's loading efficiency and encapsulation efficiency were 6.47 ± 0.10% and 71.2 ± 1.15%, respectively. According to the pharmacokinetic results, compared with free HI-6 and LP-HI-6, the intravenous injection of PEG-LP-HI-6 significantly extended t1/2 (1.47 ± 0.29 h), MRT (1.44 ± 0.07 h), and improved the AUC of HI-6 in vivo. Drug concentrations in the CNS also increased after the intravenous administration of PEG-LP-HI-6. For in vivo treatment study, twenty minutes after poison exposure, the survival rate of animals in saline, free HI-6, LP-HI-6 and PEG-LP-HI-6 groups were 0, 0, 30% and 70%, respectively. Compared with the non-PEGylated liposomes group and free HI-6, PEG-LP-HI-6 could prolong the survival time of experimental animals and alleviate the neurotoxic symptoms, which demonstrated great potential as a first-aid strategy for acute organophosphorus agent poisoning.
Keywords: Drug delivery system; intoxication; nerve agents.