Rationale: To meet the need of long-acting analgesia in postoperative pain management, slow-releasing formulations of local anesthetics (LAs) have been extensively investigated. However, challenges still remain in obtaining such formulations in a facile and cost-effective way, and a mechanism for controlling the release rate to achieve an optimal duration is still missing./nMethods: In this study, nanosheets formed by a self-assembling peptide were used to encapsulate ropivacaine in a soft-coating manner. By adjusting the ratio between the peptide and ropivacaine, ropivacaine particles with different size were prepared. Releasing profile of particles with different size were studied in vitro and in vivo. The influence of particle size and ropivacaine concentration on effective duration and toxicity were evaluated in rat models./nResults: Our results showed that drug release rate became slower as the particle size increased, with particles of medium size (2.96 ± 0.04 μm) exhibiting a moderate release rate and generating an optimal anesthetic duration. Based on this size, formulations at different ropivacaine concentrations generated anesthetic effect with different durations in rat sciatic nerve block model, with the 6% formulation generated anesthetic duration of over 35 h. Long-acting analgesia up to 48 h of this formulation was also confirmed in a rat total knee arthroplasty model./nConclusion: This study provided a facile strategy to prepare LA particles of different size and revealed the relationship between particle size, release rate and anesthetic duration, which provided both technical and theoretical supports for developing long-acting LA formulations with promising clinical application.

中文翻译：

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通过肽纳米片软涂层控制罗哌卡因纳米/微粒的尺寸以实现长效镇痛

理由：为了满足术后疼痛管理中长效镇痛的需要，局部麻醉剂（LA）的缓释制剂已被广泛研究。然而，以简便且经济有效的方式获得此类制剂仍然存在挑战，并且仍然缺乏控制释放速率以实现最佳持续时间的机制。/n方法：在本研究中，通过自组装形成的纳米片肽以软包被的方式封装罗哌卡因。通过调整肽与罗哌卡因的比例，制备出不同粒径的罗哌卡因颗粒。研究了不同粒径颗粒的体外和体内释放曲线。在大鼠模型中评估了粒径和罗哌卡因浓度对有效持续时间和毒性的影响。/n结果：我们的结果表明，随着粒径的增加，药物释放速率变慢，中等尺寸的颗粒（2.96±0.04μm）表现出药物释放速率适度的释放速率并产生最佳的麻醉持续时间。基于此尺寸，不同罗哌卡因浓度的制剂在大鼠坐骨神经阻滞模型中产生不同持续时间的麻醉效果，其中6%制剂产生的麻醉持续时间超过35小时。该制剂的长效镇痛效果长达 48 小时，在大鼠全膝关节置换术模型中也得到证实。/n结论：本研究提供了一种制备不同尺寸 LA 颗粒的简便策略，并揭示了颗粒尺寸、释放速率和镇痛效果之间的关系。麻醉持续时间，为开发具有临床应用前景的长效LA制剂提供了技术和理论支持。