Department of Mechanical Engineering, 14434University of Utah, Salt Lake City, UT, USA.
Rebel Medicine Inc., Salt Lake City, UT, USA.
J Biomater Appl. 2022 Oct;37(4):724-736. doi: 10.1177/08853282221106486. Epub 2022 Jun 1.
Proper pain management is well understood to be one of the fundamental aspects of a healthy postoperative recovery in conjunction with mobility and nutrition. Approximately, 10% of patients prescribed opioids after surgery continue to use opioids in the long-term and as little as 10 days on opioids can result in addiction. In an effort to provide physicians with an alternative pain management technique, this work evaluates the material properties of a novel local anesthetic delivery system designed for controlled release of bupivacaine for 72 hours. The formulation utilizes solid-lipid microparticles that encapsulate the hydrophobic molecule bupivacaine in its free-base form. The lipid microparticles are suspended in a non-crosslinked hyaluronic acid hydrogel, which acts as the microparticle carrier. Two different particle manufacturing techniques, milling and hot homogenization, were evaluated in this work. The hot homogenized particles had a slower and more controlled release than the milled particles. Rheological techniques revealed that the suspension remains a viscoelastic fluid when loaded with either particle type up to 25% (w/v) particles densities. Furthermore, the shear thinning properties of the suspension media, hyaluronic acid hydrogel, were conserved when bupivacaine-loaded solid-lipid microparticles were loaded up to densities of 25% (w/v) particle loading. The force during injection was measured for suspension formulations with varying hyaluronic acid hydrogel concentrations, particle densities, particle types and particle sizes. The results indicate that the formulation viscosity is highly dependent on particle density, but hyaluronic acid hydrogel is required for lowering injection forces as well as minimizing clogging events.
妥善的疼痛管理与活动能力和营养一样，是健康术后康复的基本方面之一。大约有 10%的术后开处阿片类药物的患者会长期使用阿片类药物，而仅仅使用 10 天的阿片类药物就可能导致成瘾。为了给医生提供一种替代的疼痛管理技术，这项工作评估了一种新型局部麻醉剂递送系统的材料特性，该系统旨在控制布比卡因 72 小时的释放。该配方利用固态脂质微粒，将疏水分子布比卡因以游离碱的形式包裹在其中。脂质微粒悬浮在非交联透明质酸水凝胶中，作为微粒载体。在这项工作中，评估了两种不同的颗粒制造技术，即研磨和热熔匀化。热熔匀化的颗粒比研磨的颗粒具有更慢和更受控的释放。流变技术表明，当悬浮液中负载两种颗粒类型（高达 25%（w/v）的颗粒密度）时，悬浮液仍保持为粘弹性流体。此外，当负载布比卡因的固态脂质微粒的密度高达 25%（w/v）时，悬浮液介质透明质酸水凝胶的剪切稀化特性得以保留。测量了不同透明质酸水凝胶浓度、颗粒密度、颗粒类型和颗粒大小的悬浮液制剂的注射力。结果表明，制剂的粘度高度依赖于颗粒密度，但透明质酸水凝胶对于降低注射力以及最小化堵塞事件也是必需的。
