文献类型：期刊文献

英文题名：Development of cocaine esterase W/O/W nanoemulsions by a novel low-temperature double emulsification approach for cocaine abuse treatment

作者：Wang, Weimin[1];Deng, Xingyu[2];Xu, Nuo[1];Li, Hualing[1];Lai, Suitian[4];Li, Zhenzhen[1];Hu, Qi[1];Chi, Man[1];Liu, Fengling[1];Ma, Lei[2];Liu, Junjun[4];Chen, Wenwen[3];Hou, Shurong[1];Chen, Xiabin[1]

机构：[1]Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Zhejiang, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[3]Westlake Univ, Sch Life Sci, Hangzhou 310000, Zhejiang, Peoples R China;[4]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Pharm, Wuhan 430030, Hubei, Peoples R China

年份：2025

卷号：316

外文期刊名：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

收录：;EI(收录号：20252218527311);WOS:【SCI-EXPANDED(收录号:WOS:001718029500001)】；

语种：英文

外文关键词：Cocaine esterase; Enzyme preparations; Nanoemulsions; Detoxification; Stability; Half-life

摘要：Cocaine esterase is highly effective against cocaine but has a short in vivo half-life and is sensitive to temperature, limiting its clinical use. Encapsulation of cocaine esterase in water-in-oil-in-water (W/O/W) nanoemulsions offers a promising approach to improve its stability and therapeutic effectiveness. In this study, we developed a novel low-temperature double emulsification method to encapsulate the cocaine esterase mutant (E196-301) into W/O/W nanoemulsions (designated as CocE NEs). The oil phase, containing phospholipids, was cooled to room temperature under high-speed stirring before the enzyme-containing aqueous phase was added. This process prevented the precipitation of soybean phospholipids and preserved over 90 % of E196-301's enzymatic activity. Notably, the temperature stability of E196-301 has been greatly improved, E196-301 within the inner aqueous phase maintained over 90 % of its activity under temperature variations between 37 degrees C and 40 degrees C. Importantly, the in vivo half-life of E196-301 increased from 16.26 +/- 1.94 min to 57.25 +/- 14.71 min (3 mg/kg, i.v.). Pharmacodynamic studies revealed CocE NEs (3 mg/kg, i.v.) significantly reduced cocaine-induced locomotor sensitization in mice within 45 min, by attenuating cocaine-induced (25 mg/kg, i.p.) dopamine signaling in the brain. CocE NEs represent a promising candidate for the sustained prevention and treatment of cocaine abuse.