HI-6-loaded PEGylated liposomes: an on-site first-aid strategy for acute organophosphorus agent poisoning

Abstract

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 t_1/2 (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.

Graphical Abstract

Keywords:

• Drug delivery system
• nerve agents
• intoxication

Acknowledgments

We thank Dr. Ying-Jie Zhu for her helpful comments and suggestions.

Data availability statement

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

The authors report no conflicts of interest in this work.

Ethical approval

All animal experiments complied with the regulations of the Animal Care and Use Ethics Committee of the Beijing Institute of Pharmacology and Toxicology.

Additional information

Funding

This work was supported by the Special Fund for Military Medical Science (grant numbers AWS17J009, and BWS16J007).