Department of Surgery, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132, USA.
Department of Surgery, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132, USA.
Int J Pharm. 2020 Oct 15;588:119703. doi: 10.1016/j.ijpharm.2020.119703. Epub 2020 Jul 30.
The purpose of this research was to evaluate a novel long-acting bupivacaine delivery system for control of postoperative pain. Bupivacaine-loaded lipid emulsion (BLE) droplets were created by high-speed homogenization. The BLE droplets were then entrapped into a crosslinked-hyaluronic acid hydrogel system to create an injectable composite gel formulation (HA-BLE). Dynamic light scattering, rheological, and drug release techniques were used to characterize the formulations. A rat sciatic nerve block with a thermal nociceptive assay was used to evaluate the anesthetic effect in comparison to controls, bupivacaine HCl and liposomal bupivacaine. The BLE droplets had a zeta potential, droplet size, and polydispersity index of -40.8 ± 0.66 mV, 299 ± 1.77 nm, and 0.409 ± 0.037, respectively. The HA-BLE formulation could be injected through 25 g needles and had an elastic modulus of 372 ± 23.7 Pa. Approximately 80% and 100% of bupivacaine was released from the BLE and HA-BLE formulations by 20 and 68 h, respectively. The HA-BLE formulation had a 5-times greater anesthetic area under the curve and an anesthetic duration that was twice as long as controls. Results indicate that incorporating the BLEs into the hydrogel significantly increased anesthetic effect by protecting the BLE droplets from the in vivo environment.
本研究旨在评估一种新型的布比卡因长效递送系统，以控制术后疼痛。通过高速匀浆制备载布比卡因的脂质乳剂（BLE）液滴。然后将 BLE 液滴包封在交联透明质酸水凝胶系统中，制成可注射的复合凝胶制剂（HA-BLE）。采用动态光散射、流变和药物释放技术对制剂进行了表征。通过大鼠坐骨神经阻滞和热伤害感受试验，与对照组、盐酸布比卡因和脂质体布比卡因进行比较，评估了麻醉效果。BLE 液滴的 ζ 电位、粒径和多分散指数分别为-40.8±0.66 mV、299±1.77nm 和 0.409±0.037。HA-BLE 制剂可通过 25 g 针头注射，弹性模量为 372±23.7 Pa。BLE 和 HA-BLE 制剂分别在 20 和 68 h 时释放了约 80%和 100%的布比卡因。HA-BLE 制剂的麻醉曲线下面积增加了 5 倍，麻醉持续时间延长了 2 倍，与对照组相比。结果表明，将 BLE 纳入水凝胶中可通过保护 BLE 液滴免受体内环境的影响，显著提高麻醉效果。
