装载利多卡因的可注射水凝胶对急性切口痛小鼠术后镇痛时效的影响  

Effect of loaded lidocaine injectable hydrogel on postoperative analgesic duration in mice with acute incision pain

作　　者：王郭洁颖 王迎斌[2] 刘伟[2] 桂铭鸿 牛永慧 刘璐[1] WANG Guojieying;WANG Yingbin;LIU Wei;GUI Minghong;NIU Yonghui;LIU Lu(The Second Clinical Medical College of Lanzhou University,Lanzhou 730000,China;Department of Anesthesiology,Lanzhou University Second Hospital,Lanzhou 730030,China)

机构地区：[1]兰州大学第二临床医学院,甘肃兰州730000 [2]兰州大学第二医院麻醉科,甘肃兰州730030

出　　处：《中国病理生理杂志》2025年第1期114-122,共9页Chinese Journal of Pathophysiology

基　　金：甘肃省自然科学基金资助项目(No.22JR5RA980);兰州大学第二医院“萃英科技创新”计划资助项目(No.CY2023-BJ-11)。

摘　　要：目的:探究可注射载药水凝胶盐酸利多卡因(lidocaine,LDC)/倍他米松磷酸钠水凝胶(betamethasone sodium phosphate hydrogel,BetP-Gel)对药物的持续稳定缓释作用,以及对急性切口痛模型小鼠镇痛时效的影响。方法:采用简单混合法制备载药水凝胶LDC/BetP-Gel,对其理化特性进行表征,利用正电子发射计算机断层显像(positron emission tomography/computed tomography,PET-CT)及压力变化评估其体内成胶性与可注射性。以直接释放法检测其体外释放速率,以剩余重量法测定其降解速率。将30只BALB/c小鼠随机分为5组:空白(blank)组、模型(model)组、利多卡因(4%LDC)组、水凝胶(BetP-Gel)组和利多卡因水凝胶(4%LDC/BetP-Gel)组,每组6只。采用Up-Down法和Hargreave法进行疼痛行为测定,HE染色检测生物相容性,酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)测定炎症因子的表达水平。结果:所制备的LDC/BetP-Gel展现出良好的药物负载与持续缓释能力。行为学检测显示,与model组相比,LDC/BetP-Gel组小鼠的痛阈提升(P<0.05),减轻术后疼痛的效果显著;与4%LDC组相比,LDC/BetP-Gel组的镇痛时间显著延长(P<0.05)。HE染色结果证实其生物相容性好。ELISA结果显示,与model组和4%LDC组相比,4%LDC/BetP-Gel组术后24 h内炎性因子表达水平显著降低(P<0.05)。结论:可注射水凝胶LDC/BetP-Gel具有致密稳定的结构,可实现药物搭载及缓释效果,并且在足底急性切口痛模型小鼠中验证了延长抗炎镇痛时效的能力。AIM:This study aims to investigate the sustained and stable drug release profile of the injectable hydrogel lidocaine(LDC)/betamethasone sodium phosphate hydrogel(BetP-Gel)and its effect on analgesic duration in a mouse model of acute incisional pain.METHODS:The drug-loaded hydrogel LDC/BetP-Gel was prepared through a simple mixing process.Its physicochemical properties were characterized using electron microscopy,X-ray diffraction,Fourier-transform infrared spectroscopy,and rheological testing.In vivo gelation and injectability were evaluated through positron emission tomography/computed tomography(PET-CT)imaging and pressure variation measurements.The in vitro drug release rate was determined using a direct release method,while the degradation rate was assessed using the residual weight method.A total of thirty BALB/c mice were randomly assigned to five groups:blank group,model group,4%LDC group,BetP-Gel group,and 4%LDC/BetP-Gel group.Pain behavior was assessed using the Up-Down method and Hargreave's test.Biocompatibility was evaluated through HE staining,and the expression levels of inflammatory cytokines were measured via enzyme-linked immunosorbent assay(ELISA).RESULTS:The LDC/BetP-Gel hydrogel demonstrated excellent drug encapsulation and sustained release properties.Behavioral assessments indicated that the LDC/BetP-Gel group exhibited significantly higher pain thresholds compared to the model group(P<0.05),suggesting improved postoperative pain relief.Furthermore,the LDC/BetP-Gel group showed a markedly prolonged analgesic effect compared to the LDC group(P<0.05).HE staining confirmed the biocompatibility of the hydrogel.ELISA results revealed a significant reduction in inflammatory cytokine levels in the LDC/BetP-Gel group 24 hours post-surgery(P<0.05).CONCLUSION:The injectable hydrogel LDC/BetP-Gel possesses a dense and stable structure that enables effective drug loading and sustained release.Its ability to prolong anti-inflammatory and analgesic effects has been validated in a mouse model of acute in

关 键 词：术后疼痛 多模式镇痛 可注射水凝胶 利多卡因 倍他米松 

分 类 号：R614.3[医药卫生—麻醉学] R441.1[医药卫生—外科学] R363[医药卫生—临床医学]