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载 HI-6 的聚乙二醇化脂质体：用于急性有机磷中毒的现场急救策略。

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

机构信息

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

出版信息

Drug Deliv. 2023 Dec;30(1):20-27. doi: 10.1080/10717544.2022.2152132.

DOI:10.1080/10717544.2022.2152132
PMID:36452996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9721435/
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 (1.47 ± 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.

摘要

有机磷化合物，又称神经毒剂，是非常危险的化学物质，曾被用作化学战剂。HI-6 是最有前途的重活化剂之一，可有效重活化被许多神经毒剂抑制的 AChE。然而，HI-6 在体内的快速清除率在某些复杂情况下成为急救使用的一大障碍。在这项研究中，制备了载有 HI-6 的聚乙二醇化脂质体并进行了体外和体内评价。对于 PEG-LP-HI-6，最佳制剂的载药效率和包封效率分别为 6.47±0.10%和 71.2±1.15%。根据药代动力学结果，与游离 HI-6 和 LP-HI-6 相比，PEG-LP-HI-6 的静脉注射明显延长了 t（1.47±0.29 h）、MRT（1.44±0.07 h），并改善了 HI-6 在体内的 AUC。静脉注射 PEG-LP-HI-6 后，CNS 中的药物浓度也增加了。在体内治疗研究中，中毒后 20 分钟，盐水、游离 HI-6、LP-HI-6 和 PEG-LP-HI-6 组动物的存活率分别为 0、0、30%和 70%。与非聚乙二醇化脂质体组和游离 HI-6 相比，PEG-LP-HI-6 可以延长实验动物的存活时间并减轻神经毒性症状，这表明它作为急性有机磷中毒急救策略具有很大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/8b7166aca4db/IDRD_A_2152132_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/23566f79bdf2/IDRD_A_2152132_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/65c9f49f57ad/IDRD_A_2152132_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/e7050d48e19c/IDRD_A_2152132_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/6efb00dc1e6d/IDRD_A_2152132_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/552d8a3d53e3/IDRD_A_2152132_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/328cdd34ada2/IDRD_A_2152132_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/8b7166aca4db/IDRD_A_2152132_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/23566f79bdf2/IDRD_A_2152132_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/65c9f49f57ad/IDRD_A_2152132_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/e7050d48e19c/IDRD_A_2152132_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/6efb00dc1e6d/IDRD_A_2152132_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/552d8a3d53e3/IDRD_A_2152132_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/328cdd34ada2/IDRD_A_2152132_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de6/9721435/8b7166aca4db/IDRD_A_2152132_F0006_C.jpg

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