Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.
Center for Surgical Research, University Hospital Zurich, University Zurich, Zurich, Switzerland.
Sci Rep. 2020 Oct 14;10(1):17295. doi: 10.1038/s41598-020-74230-6.
Buprenorphine is a frequently used analgetic agent in veterinary medicine. A major drawback, however, is the short duration of action requiring several daily administrations. We therefore designed a poly-lactic-co-glycolic acid (PLGA) based microparticulate drug formulation for sustained parenteral drug release. Particles were designed to allow for a fast onset of action and a duration of the analgesic effect of at least two days in laboratory mice. Microparticles were produced using a solvent evaporation technique. Release rate was dependent on polymer type and particle size. Spherical particles used for subsequent animal studies had a mean size of 50 µm and contained 4.5% of buprenorphine. Drug release was characterized by an initial burst release of 30% followed by complete release over seven days. In vivo pharmacokinetic experiments in female C57BL/6 J mice confirmed prolonged exposure in plasma and brain tissue and correlated with the pharmacological effect in the hot plate assay or after minor abdominal surgery. No adverse side effects with respect to food and water intake, body weight, local tolerability, or nesting behavior were observed. Our formulation is an attractive alternative to established immediate release formulations. A use for prolonged pain management in laboratory animals is proposed.
丁丙诺啡是兽医中常用的一种镇痛药。然而，其主要缺点是作用持续时间短，需要每日多次给药。因此，我们设计了一种基于聚乳酸-共-羟基乙酸（PLGA）的微粒药物制剂，用于持续的药物释放。这些微粒旨在使药物迅速起效，并在实验室小鼠中至少持续两天的镇痛作用。采用溶剂蒸发技术制备微粒。释放率取决于聚合物类型和粒径。用于后续动物研究的球形微粒的平均粒径为 50μm，含有 4.5%的丁丙诺啡。药物释放特征是初始突释 30%，然后在七天内完全释放。在雌性 C57BL/6J 小鼠中的体内药代动力学实验证实了在血浆和脑组织中的延长暴露，并与热板试验或小腹部手术后的药理作用相关。未观察到与食物和水摄入、体重、局部耐受性或筑巢行为相关的不良副作用。我们的制剂是一种有吸引力的替代现有速释制剂的选择。拟用于实验室动物的长期疼痛管理。
