基于复合多聚体材料的缓释局麻药在慢性痛动物模型中的应用

  目的  对复合多聚体材料组成的局麻药缓释载体的药物释放特征和镇痛效果进行测评。  方法  使用静电纺丝技术制备含盐酸布比卡因的PLGA(聚乳酸-羟基乙酸共聚物)缓释膜(静电纺丝膜, M组), 并以PLGA-PEG(聚乙二醇)-PLGA温敏凝胶包裹纺丝膜制备成含盐酸布比卡因的缓释递送系统(凝胶包裹静电纺丝膜形成的复合缓释载体, G组), 评定两组体外释放特征、体内镇痛效果及安全性。  结果  体外条件下, M组对盐酸布比卡因的累积释放时间可达5 d以上, G组累积释放时间可延长至10 d。体内条件下, M组和G组对坐骨神经慢性压迫损伤大鼠模型的镇痛时间均可达14 d, 两组镇痛效果无显著差异(P＞0.05)。M组盐酸布比卡因血药浓度在术后第1天达峰值(0.294±0.029)μg/L], G组于术后第3天达峰值(0.192±0.064)μg/L], 且峰值较M组降低, 两组盐酸布比卡因血药浓度均在安全范围内。HE染色示, M组、G组大鼠的心脏、肝脏、脾脏、肺、肾脏组织均未见明显病理改变。  结论  本研究制备的以盐酸布比卡因纳米纺丝缓释膜为基础, PLGA-PEG-PLGA温敏凝胶包裹为介质的复合缓释材料, 可进一步延长盐酸布比卡因缓释时间, 具有长效镇痛效果且无毒性作用。

Application of Extended-release Local Anesthetics Based on Composite Polymer Materials in an Animal Model of Chronic Pain

  Objective  To evaluate the release characteristics and analgesic effect of extended-release composite polymers of local anesthetics.  Methods  Polymer extended-release film containing bupivacaine hydrochloride was prepared via electrospinning (nanomembrane, group M), and was furthermore loaded intoPLGA-PEG-PLGA thermo-sensitive gel forming composite extended-release carrier (group G). The in vitro release profile, analgesic effect and safety in vivo were evaluated.  Results  In vitro, the cumulative release of bupivacaine hydrochloride reached more than 5 d in the group M and 10 d in the group G. In vivo, the analgesic effect in the model of chronic compression injury of sciatic nerve lasted for 14 d in the group M and group G. There was no significant difference between the two groups (P > 0.05). The peak plasma concentration of bupivacaine hydrochloride in the group M was (0.294±0.029)μg/L one day after drug administration, while (0.192±0.064)μg/L in the group G three days after drug administration, which were far below the toxic plasma level of bupivacaine chloride. Meanwhile, there were no significant pathological changes in the heart, liver, spleen, lung and kidney of the two groups.  Conclusions  In this study, the composite extended-release drug delivery prepared by bupivacaine hydrochloride electrospinning film as the basis and PLGA-PEG-PLGA thermo-sensitive gel can further prolong the release time of bupivacaine chloride and exhibit long-term analgesic effect without toxicity.