title: Effects of Liposomes Charge on Extending Sciatic Nerve Blockade of N-ethyl Bromide of Lidocaine in Rats.
abstract: N-methyl bromide of lidocaine (QX-314) is a potential local anaesthetic with compromised penetration through cell membranes due to its obligated positive charge. Liposomes have been widely used for drug delivery with promising efficacy and safety. Therefore we investigated the local anaesthetic effects and tissue reactions of QX-314 in combination with anionic, cationic or neutral liposomes in rat sciatic nerve block model, and explored the effects of these liposomes on cellular entry of QX-314 in human embryonic kidney 293 cells. The results demonstrated that anionic liposomes substantially prolonged the duration of sensory (25.7 ± 8.3 h) and motor (41.4 ± 6.1 h) blocks of QX-314, while cationic and neutral ones had little effects. Tissue reactions from QX-314 with anionic liposomes were similar to those with commonly used local anaesthetic bupivacaine. Consistent with in vivo results, the anionic liposomes produced the greatest promotion of cellular entry of QX-314 in a time-dependent manner. In conclusion, ultra-long lasting nerve blocks were achieved by a mixture of QX-314 and anionic liposomes with a satisfactory safety profile, indicating a potential approach to improve postoperative pain management. The liposome-induced enhancement in cellular uptake of QX-314 may underlie the in vivo effects.
authors.affiliation: Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Ke
authors.affiliation: National Engineering Research Centre for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Institution of Clinical Trials, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Feng
authors.affiliation: Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Centre of West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.|Department of Anaesthesiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, P.R. China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Engineering Research Centre for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nie
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D007150:Immunohistochemistry; D008012:Lidocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D008081:Liposomes; D015394:Molecular Structure; D009407:Nerve Block; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D008081:Liposomes; C012647:QX-314; D008012:Lidocaine