Classical local anesthetics are unsuitable to treat regional pain lasting several days due to their limited duration and systemic toxicity. Self-delivery nano systems without excipients were designed for long-term sensory blocks. 1a self-assembled into different vehicles with different fractions of intermolecular π–π stacking, transported itself into nerve cells, and released single molecules slowly to achieve long-term duration for rats’ sciatic nerve block for 11.6 h in water, 12.1 h in water with CO₂ and 3.4 h in NS (normal saline). After the counter ions were changed to SO₄²⁻, 1e can self-assemble into vesicles and prolong the duration to 43.2 h, which was much longer than the 3.8 h led by (s)-bupivacaine hydrocloride (0.75%). This was mainly caused by the enhancement of self-release and counter ion exchange inside nerve cells, which were affected by the gemini surfactant structure, pK_a of the counter ions and π–π stacking interactions.

中文翻译：

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由自我递送局部麻醉纳米系统的超分子排列主导的长期坐骨神经阻滞

由于其持续时间有限且具有全身毒性，经典局部麻醉剂不适合治疗持续数天的局部疼痛。不含赋形剂的自递送纳米系统专为长期感觉障碍而设计。1a自组装成具有不同分子间π-π堆积比例的不同载体，将自身转运到神经细胞中，并缓慢释放单分子，实现大鼠坐骨神经阻滞的长期持续时间，水中11.6小时，水中12.1小时在 NS（生理盐水）中用 CO _{2和 3.4 小时。}当抗衡离子变为SO ₄ ²⁻后，1e可以自组装成囊泡，并将持续时间延长至43.2 h，远长于( s )导致的3.8 h)-盐酸布比卡因 (0.75%)。这主要是由于神经细胞内自我释放和抗衡离子交换的增强，受到双子表面活性剂结构、抗衡离子的p K _{a和π-π堆积相互作用的影响。}