摘要
背景:研究组采用乳化溶剂挥发O/W法制备了包裹罗哌卡因的聚乙二醇/聚乳酸微球,体外实验显示其具有良好的药效学与缓释性能。目的:进一步观察包裹罗哌卡因的聚乙二醇/聚乳酸微球的体内缓释性能与组织相容性。方法:采用乳化溶剂挥发O/W法制备包裹罗哌卡因的聚乙二醇/聚乳酸微球。将150只雄性Wistar大鼠(由四川省医学科学院四川省人民医院实验动物研究所提供)随机分3组处理:空白对照组(n=50)一侧坐骨神经周围间隙植入未包裹罗哌卡因的聚乙二醇/聚乳酸微球,普通药物组(n=50)一侧坐骨神经周围间隙注射盐酸罗哌卡因,缓释药物组一侧坐骨神经周围间隙植入包裹罗哌卡因的聚乙二醇/聚乳酸微球,普通药物组与缓释药物组的罗哌卡因剂量相同。给药后10,30 min及1,3,5,7,10,15,30,48 h,利用热踏板实验评估大鼠坐骨神经感觉阻滞情况,提尾实验观察大鼠坐骨神经运动阻滞情况,高效液相色谱分析血浆中罗哌卡因浓度;术后1周,检测各组大鼠体质量变化,组织学观察坐骨神经组织与其周围肌肉组织及心、肝、肺、肾、脾等重要脏器的病理变化。实验已获得四川省医学科学院四川省人民医院实验动物研究所伦理委员会批准。结果与结论:①普通药物组给药后30 min后出现坐骨神经感觉与运动阻滞,7 h时感觉阻滞消失,10 h时神经阻滞消失;缓释药物组给药后3 h出现坐骨神经感觉与运动阻滞,48 h时神经阻滞消失;②普通药物组血浆罗哌卡因浓度逐渐升高,至给药1 h时药物浓度到达峰值,随后开始下降且较迅速,至7 h时已检测不到;缓释药物组药物浓度逐渐升高,至3 h时上升幅度较大,至10 h时达到峰值,随后逐渐降低,至48 h维持在较低的浓度;③缓释药物组大鼠未出现呼吸抑制、惊厥、窒息或死亡等中毒表现,切口均正常愈合,大鼠体质量增加值未受影响,心、肝、肺、肾、脾等重要脏器均未见明显的结构异常与病理改变,给药侧肌肉组织未见明显的坏死、感染与组织纤维化,神经组织也未见明显病理变化;③结果表明,包裹罗哌卡因的聚乙二醇/聚乳酸微球具有良好的动物体内缓释性能与组织相容性。
BACKGROUND:The polyethylene glycol/polylactic acid(PEG/PLA)microspheres encapsulated by ropivacaine were prepared by oil in water emulsion solvent evaporation method.In vitro experiments showed that the prepared PEG/PLA microspheres have good pharmacodynamics and in vitro sustained release performance.OBJECTIVE:To further investigate the in vivo sustained-release properties and histocompatibility of PEG/PLA microspheres encapsulated by ropivacaine.METHODS:PEG/PLA microspheres encapsulated by ropivacaine were prepared by oil in water O/W emulsion solvent evaporation method.A total of 150 male Wistar rats were provided by Laboratory Animal Center of Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,China and randomly divided into three groups(n=50/group).In the blank control group,PEG/PLA microspheres without ropivacaine encapsulation were implanted into the space surrounding the sciatic nerve on one side.In the common drug group,ropivacaine hydrochloride was injected into the space surrounding the sciatic nerve.In the sustained release drug group,PEG/PLA microspheres encapsulated by ropivacaine were implanted into the same region.The dose of ropivacaine used in the common drug and ropivacaine hydrochloride groups was the same.At 10 and 30 minutes,1,3,5,7,10,15,30 and 48 hours after drug administration,the sensory block of rat sciatic nerve was evaluated by hot pedal test,the motor block of the sciatic nerve was observed by tail-lifting test,and serum concentration of ropivacaine was analyzed by high performance liquid chromatography.At 1 week after surgery,change in rat body mass was evaluated,and the pathological changes of rat sciatic nerve as well as its surrounding tissue and the important organs such as the heart,liver,lung,kidney,and spleen were observed.This study was approved by the Animal Ethics Committee of Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital.RESULTS AND CONCLUSION:In the common drug group,sciatic nerve sensory and motor block appeared 30 minutes after drug administration.The sensory block disappeared at 7 hours,and the nerve block disappeared at 10 hours.In the sustained-release drug group,sciatic nerve sensory and motor block occurred 3 hours after drug administration,and the nerve block disappeared at 48 hours.In the common drug group,serum concentration of ropivacaine gradually increased,peaked at 1 hour after drug administration,then rapidly decreased,and was non-detectable at 7 hours.In the sustained-release drug group,serum concentration of ropivacaine was gradually increased to a greater extent at 3 hours,peaked at 10 hours,then gradually decreased,and maintained at a relatively low concentration at 48 hours.In the drug sustained-release group,no respiratory depression,convulsion,asphyxia or death were observed.In addition,incisions healed normally,the increase in body mass was not affected.No obvious structural abnormalities and pathological changes were observed in important organs such as the heart,liver,lung,kidney and spleen.No obvious necrosis,infection and tissue fibrosis were observed in the muscle tissue on the donor side.No obvious pathological changes were observed in the nerve tissue.These results suggest that PEG/PLA microspheres encapsulated by ropivacaine have good sustained-release properties and histocompatibility in vivo.
作者
吴波
李祥奎
王华
文之远
Wu Bo;Li Xiangkui;Wang Hua;Wen Zhiyuan(Department of Anesthesiology,Modern Hospital of Sichuan,Chengdu 610041,Sichuan Province,China;Department of Anesthesiology,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Chengdu 610072,Chengdu Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2019年第34期5486-5491,共6页
Chinese Journal of Tissue Engineering Research
关键词
罗哌卡因
聚乙二醇/聚乳酸微球
缓释性能
组织相容性
坐骨神经
缓释微球
坐骨神经阻滞
坐骨神经
ropivacaine
polyethylene glycol/polylactic acid microspheres
sustained release performance
histocompatibility
sciatic nerve
sustained-release microscope
sciatic nerve block
sciatic nerve
