Precision-guided long-acting analgesia by Gel-immobilized bupivacaine-loaded microsphere.
Precision-guided long-acting analgesia by Gel-immobilized bupivacaine-loaded microsphere.
复制标题
凝胶固定布比卡因微球精准引导长效镇痛
作者：
Zhang W;Ning C;Xu W;Hu H;Li M;Zhao G;Ding J;Chen X
周围神经阻滞（PNB）是一种传统的战略管理急性术后疼痛。然而，由于局部麻醉药的低分子量，其镇痛持续时间短和潜在的全身毒性限制了其应用。研究方法：制备了一种可注射的凝胶微球（Gel-MS）系统，该系统由PLGA-PEG-PLGA凝胶（Gel）和凝胶固定化布比卡因载药微球（MS/BUP）组成，用于精确导向的长效镇痛。通过扫描电镜、流变学、激光共聚焦扫描显微镜、药物释放、溶蚀降解等体外表征方法，考察了微球的生物相容性。在此基础上，采用坐骨神经阻滞模型评价了凝胶-微球系统的体内镇痛效果、凝胶对微球的固定效果以及系统的生物相容性。结果如下：BUP从Gel-MS系统的释放受内部MS和外部凝胶基质两者的调节，证明BUP在体外持续释放数天而没有初始突释。更重要的是，凝胶的掺入固定了MS，并由于其原位性质而阻碍了MS从注射部位的扩散，这有助于高局部药物浓度并防止全身副作用。在体内，单次注射Gel-MS/BUP使大鼠维持感觉和运动阻滞的时间显著长于MS/BUP（P < 0.01）或负载BUP的凝胶（Gel-BUP，P < 0.01）。组织学结果表明，凝胶-MS系统具有良好的生物降解性和生物相容性，无神经毒性。结论：这种精确指导的长效镇痛，它提供了一个原位和持续释放的BUP，是一个有前途的策略，长效镇痛，并可能代表一个潜在的替代临床疼痛管理。
Peripheral nerve blockade (PNB) is a conventional strategy for the management of acute postoperative pain. However, the short duration of the associated analgesia and the potential systemic toxicity due to the low molecular weights of local anesthetics limit their application. Methods: An in situ forming injectable Gel-microsphere (Gel-MS) system consisting of PLGA-PEG-PLGA Gel (Gel) and Gel-immobilized bupivacaine-loaded microsphere (MS/BUP) was prepared for precision-guided long-acting analgesia. A series of in vitro characterizations, such as scanning electron microscopy, rheology analysis, confocal laser scanning microscopy, drug release, and erosion and degradation, were carried out. After that, the in vivo analgesia effect of the Gel-MS system, the immobilization effect of Gel on the MS, and biocompatibility of the system were evaluated using a sciatic nerve block model. Results: The BUP release from the Gel-MS system was regulated by both the inner MS and the outer Gel matrix, demonstrating sustained BUP release in vitro for several days without an initial burst release. More importantly, incorporation of the Gel immobilized the MS and hindered the diffusion of MS from the injection site because of its in situ property, which contributed to a high local drug concentration and prevented systemic side effects. In vivo, a single injection of Gel-MS/BUP allowed rats to maintain sensory and motor blockade significantly longer than treatment with MS/BUP (P < 0.01) or BUP-loaded Gel (Gel-BUP, P < 0.01). Histopathological results demonstrated the excellent biodegradability and biocompatibility of the Gel-MS system without neurotoxicity. Conclusion: This precision-guided long-acting analgesia, which provides an in situ and sustained release of BUP, is a promising strategy for long-acting analgesia, and could represent a potential alternative for clinical pain management.
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