一种基于油凝胶的可注射布比卡因配方,用于延长非阿片类药物术后镇痛。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-08-06 DOI:10.1007/s13346-024-01688-6
Susan Wojtalewicz, Jack Shuckra, Keelah Barger, Sierra Erickson, Jonathon Vizmeg, Stefan Niederauer, Andrew Simpson, Jordan Davis, Avital Schauder, Orna Hifi, David Castel, Sigal Meilin, Jayant Agarwal, Caleb Lade, Brett Davis
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引用次数: 0

摘要

阿片类药物仍然是术后疼痛治疗的主要药物,尽管这些药物存在大量不良反应,包括成瘾、恶心、便秘、认知障碍、呼吸抑制以及因过量使用而意外死亡。局麻药能有效控制手术后的剧烈疼痛,但其作用时间短,限制了其在术后疼痛治疗中的临床应用。在本手稿中,一种优化的布比卡因注射用油凝胶制剂可用于多天的术后疼痛治疗,该制剂在台式机上进行了表征,并在两个与临床相关的猪术后疼痛模型中进行了评估。台式表征验证了基于油凝胶的布比卡因制剂的优化设计,证明了均匀稳定的油凝胶具有剪切稀化特性、高载药量和一阶药物释放动力学,可在 5 天内实现充分的注射性。在两个猪术后疼痛模型中进行的体内评估表明,基于油凝胶的布比卡因配方可通过两种给药途径提供具有统计学意义的多日镇痛效果:直接在手术部位局部灌注和超声引导下的周围神经阻滞注射。ALX005 的药代动力学评估发现,当给药剂量达到盐酸布比卡因对照剂量的 2.7 倍和 8.1 倍时,其 Cmax 值与盐酸布比卡因对照组没有统计学差异,也没有观察到局部麻醉剂全身毒性的临床症状。这项研究证明了以油凝胶为基础的可注射布比卡因制剂的临床前安全性和有效性,并探讨了它作为一种单次给药的长效局麻药产品在术后疼痛治疗中的实用性,这种产品既可用于局部麻醉,也可用于区域麻醉。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

Opioid-based medications remain the mainstay of post-operative pain management, even though they are associated with a plethora of adverse effects including addiction, nausea, constipation, cognitive impairment, respiratory depression, and accidental death due to overdose. Local anesthetics are effective at controlling the intense pain after surgery but their short duration of effect limits their clinical utility in post-operative pain management. In this manuscript, an optimized injectable oleogel-based formulation of bupivacaine for multi-day post-operative pain management was characterized on the benchtop and assessed in two clinically-relevant porcine post-operative pain models. Benchtop characterization verified the optimized oleogel-based bupivacaine formulation design, demonstrating a homogenous stable oleogel with sufficient injectability due to shear-thinning properties, high drug loading capacity and first-order drug release kinetics over 5 days. In vivo assessment in two pig post-operative pain models demonstrated that the oleogel-based bupivacaine formulation can provide statistically significant multi-day analgesia in two routes of administration: local instillation directly into a surgical site and ultrasound-guided peripheral nerve block injection. Pharmacokinetic assessment of ALX005 found that Cmax values were not statistically different from the bupivacaine HCl control, with no clinical signs of local anesthetic systemic toxicity observed, when administering up to 2.7 and 8.1 times the control dose of bupivacaine HCl. This study demonstrates the pre-clinical safety and efficacy of an injectable oleogel-based bupivacaine formulation and explores its utility as a single-administration long-acting local anesthetic product for post-operative pain management that can be used in both local and regional anesthetic applications.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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