Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China.
Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China.
Int J Pharm. 2022 Jan 5;611:121291. doi: 10.1016/j.ijpharm.2021.121291. Epub 2021 Nov 12.
Reducing post-surgical pain can promote recovery of mobility, improve patient satisfaction, and reduce the risk of chronic pain syndrome. When managing post-surgical pain, single-injection local anesthesia is more convenient and involves lower risk to the patient than multi-injection regimes, but the effects are not long-lasting. Here we developed a system that can prolong local anesthesia after a single injection. In this system, ropivacaine (Ro) is encapsulated into liposomes, which are then loaded into Poloxamer 407-based thermosensitive hydrogels. The Ro-loaded liposome-in-gel system (Ro-Lip-Gel) is in a sol state before injection, and immediately after subcutaneous injection, it forms a gel in situ. We show through in vitro release and in vivo pharmacokinetics studies that this gel acts as a drug release depot. In rats, the initial burst release of Ro was smaller from Ro-Lip-Gel than from Ro solution or Ro-Gel, and Ro-Lip-Gel caused nerve blockade lasting four times longer than Ro solution. Ro-Lip-Gel degraded in vivo and showed good biocompatibility. Our results suggest that a liposome-in-gel system can show small initial burst release, long-term nerve blockade and good biocompatibility in vitro and in vivo. Therefore, such a system may be useful for sustained local anesthesia without systemic toxicity.
减少术后疼痛可以促进活动能力的恢复，提高患者满意度，并降低慢性疼痛综合征的风险。在管理术后疼痛时，与多次注射方案相比，单次注射局部麻醉更方便，对患者的风险更低，但效果持续时间不长。在这里，我们开发了一种可以延长单次注射后局部麻醉效果的系统。在该系统中，罗哌卡因（Ro）被包封在脂质体中，然后将脂质体载入泊洛沙姆 407 基热敏水凝胶中。Ro 负载脂质体-凝胶系统（Ro-Lip-Gel）在注射前呈溶胶状态，在皮下注射后立即原位形成凝胶。我们通过体外释放和体内药代动力学研究表明，该凝胶充当药物释放库。在大鼠中，与 Ro 溶液或 Ro-Gel 相比，Ro-Lip-Gel 的 Ro 初始突释较小，并且 Ro-Lip-Gel 引起的神经阻滞作用持续时间长 4 倍。Ro-Lip-Gel 在体内降解，并表现出良好的生物相容性。我们的研究结果表明，脂质体-凝胶系统在体外和体内均表现出较小的初始突释、长期的神经阻滞和良好的生物相容性。因此，这种系统可能对没有全身毒性的持续局部麻醉有用。
