Lu Jing, Tian Wenjie, Cui Linxian, Cai Bing, Zhang Tingting, Huang Nan, Lu Lei, Zhu Tao
Department of Anesthesiology, Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China.
Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Ann Transl Med. 2021 May;9(10):871. doi: 10.21037/atm-21-1930.
Lidocaine (LDC) is a local anesthetic widely used to relieve intubation-related airway responses. However, low drug concentration and short effective duration of LDC is inadequate to provide a satisfactory anesthetic effect on the surface of the airway. The present study sought to develop a LDC-delivery endotracheal tube (ETT) to achieve high local drug concentration and sustained drug release with the aim of attenuating an intubation-related airway response.
ETTs and polyvinyl chloride (PVC) discs were coated with different molecular weight (MW) poly lactic-co-glycolic acid (PLGA: 50/50; MW: 3,000, 6,000, and 10,000) loaded with LDC by airbrush spray. The morphology of LDC-eluting coatings was analyzed using scanning electron microscopy. drug release was determined by ultraviolet spectrophotometer. An study was performed to investigate the differences in plasma LDC concentration, intubation tolerance, and tracheal tissue injury in rabbits undergoing intubation of blank, LDC-spray, or LDC-coated ETTs.
Approximate 5 mg/cm coatings (containing 2.5 mg/cm LDC) were deposited onto the PVC discs and ETTs. While even distribution and smooth surfaces were generated in PLGA3000 + LDC and PLGA6000 + LDC coatings, PLGA10000 + LDC formed uneven and gullied coatings. Burst release within the first 4 h and sustained release for at least 5 days was achieved in PLGA + LDC coatings and the study demonstrated higher plasma LDC concentration and longer drug release duration in LDC-coated ETTs compared with LDC-spray. LDC-coated ETTs significantly improved intubation tolerance in rabbits, as measured by less general anesthetic consumption and longer tube tolerance duration in contrast to blank ETTs with or without LDC spray. Histology assessment showed less mucosal edema area in the PLGA3000 + LDC and PLGA6000 + LDC groups compared to the control, LDC-spray, and PLGA10000 + LDC groups. Among the different MW PLGAs, PLGA6000 presented optimal morphological characteristics, drug release, and anesthetic effect.
ETTs coated with PLGA + LDC effectively attenuate an intubation-related airway response increasing local drug concentration and extending drug action duration, which demonstrates a potential therapeutic benefit for patients undergoing intubation.
利多卡因(LDC)是一种广泛用于减轻插管相关气道反应的局部麻醉剂。然而,LDC的低药物浓度和短有效持续时间不足以在气道表面提供令人满意的麻醉效果。本研究旨在开发一种LDC输送气管内导管(ETT),以实现高局部药物浓度和持续药物释放,从而减轻插管相关气道反应。
通过喷枪喷雾将负载LDC的不同分子量(MW)聚乳酸-乙醇酸共聚物(PLGA:50/50;MW:3000、6000和10000)涂覆在ETT和聚氯乙烯(PVC)圆盘上。使用扫描电子显微镜分析LDC洗脱涂层的形态。通过紫外分光光度法测定药物释放。进行一项研究以调查接受空白、LDC喷雾或LDC涂层ETT插管的兔子在血浆LDC浓度、插管耐受性和气管组织损伤方面的差异。
约5mg/cm的涂层(含2.5mg/cm的LDC)沉积在PVC圆盘和ETT上。虽然PLGA3000 + LDC和PLGA6000 + LDC涂层形成了均匀分布和平滑表面,但PLGA10000 + LDC形成了不均匀且有沟壑的涂层。PLGA + LDC涂层在最初4小时内实现了突发释放,并持续释放至少5天,该研究表明与LDC喷雾相比,LDC涂层ETT中的血浆LDC浓度更高且药物释放持续时间更长。LDC涂层ETT显著提高了兔子的插管耐受性,与有无LDC喷雾的空白ETT相比,其全身麻醉药消耗量更少且导管耐受时间更长。组织学评估显示,与对照组、LDC喷雾组和PLGA10000 + LDC组相比,PLGA3000 + LDC和PLGA6000 + LDC组的黏膜水肿面积更小。在不同MW的PLGA中,PLGA6000呈现出最佳的形态特征、药物释放和麻醉效果。
涂有PLGA + LDC的ETT通过提高局部药物浓度和延长药物作用持续时间有效减轻了插管相关气道反应,这对接受插管的患者显示出潜在的治疗益处。