Local anesthetics are effective in relieving pain, but their duration of action is short. Therefore, the development of injectable sustained release systems to prolong the effect of local anesthetics has been of interest. In such systems delivering conventional local anesthetics, it has been challenging to achieve long durations of effect, particularly without incurring tissue toxicity. To overcome these challenges, we created a platform comprising a protein hydrogel incorporating hydrophobic local anesthetic (bupivacaine) nanoparticles. The nanoparticles were prepared by anti-solvent precipitation stabilized with bovine serum albumin (BSA), followed by crosslinking with glutaraldehyde (GA). The resulting BSA hydrogels prolonged release of bupivacaine . When bupivacaine nanoparticles within crosslinked BSA, were injected at the sciatic nerve in rats, a duration nerve block of 39.9 h was obtained, compared to 5.5 h for the commercial bupivacaine liposome suspension EXPAREL®. Tissue reaction was benign. We further demonstrated that this system could control the release of the amphiphilic drug diphenhydramine and the hydrophobic paclitaxel.

中文翻译：

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用于长时间局部麻醉的混合纳米颗粒-蛋白质水凝胶系统

局部麻醉剂可以有效缓解疼痛，但作用持续时间较短。因此，开发可注射缓释系统以延长局部麻醉药的效果一直受到关注。在这种提供传统局部麻醉剂的系统中，实现长时间的效果一直是一个挑战，特别是在不引起组织毒性的情况下。为了克服这些挑战，我们创建了一个包含疏水性局麻药（布比卡因）纳米颗粒的蛋白质水凝胶的平台。通过用牛血清白蛋白（BSA）稳定的反溶剂沉淀，然后用戊二醛（GA）交联来制备纳米颗粒。由此产生的 BSA 水凝胶可延长布比卡因的释放。当将交联 BSA 内的布比卡因纳米颗粒注射到大鼠坐骨神经时，获得了 39.9 小时的神经阻滞持续时间，而商业布比卡因脂质体悬浮液 EXPAREL® 的持续时间为 5.5 小时。组织反应是良性的。我们进一步证明该系统可以控制两亲性药物苯海拉明和疏水性紫杉醇的释放。