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盐酸利多卡因负载聚电解质复合物-泊洛沙姆温敏水凝胶:用于牙槽窝伤口给药的体外-体内麻醉评估。

Lidocaine HCl-Loaded Polyelectrolyte Complex -Poloxamer Thermoresponsive Hydrogel: In Vitro- In Vivo Anesthetic Evaluations for Tooth Socket Wound Delivery.

机构信息

Department of Oral Surgery, College of Dental Medicine, Rangsit University, Pathum Thani, 12000, Thailand.

Department of Pharmaceutical Technology, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand.

出版信息

AAPS PharmSciTech. 2024 Aug 13;25(6):182. doi: 10.1208/s12249-024-02894-8.

Abstract

Local anesthesia is essential in dental practices, particularly for managing pain in tooth socket wounds, yet improving drug delivery systems remains a significant challenge. This study explored the physicochemical characteristics of lidocaine hydrochloride (LH) incorporated into a polyelectrolyte complex and poloxamer thermosensitivity hydrogel, assessing its local anesthetic efficacy in mouse models and its onset and duration of action as topical anesthetics in clinical trials. The thermoresponsive hydrogel exhibited a rapid phase transition within 1-3 minutes and demonstrated pseudo-plastic flow behavior. Its release kinetics followed Korsmeyer-Peppas, with 50% of biodegradation occurring over 48 h. In mouse models, certain thermogels showed superior anesthetic effects, with rapid onset and prolonged action, as evidenced by heat tolerance in tail-flick and hot plate models. In clinical trials, the LH-loaded thermoresponsive hydrogel provided rapid numbness onset, with anesthesia (T) beginning at an average of 46.5 ± 22.5 seconds and lasting effectively (T) for 202.5 ± 41.0 seconds, ranging from 120 to 240 seconds, indicating sustained release. These results highlight the promising properties of these formulations: rapid onset, prolonged duration, mucoadhesion, biodegradability, and high anesthesia effectiveness. This study demonstrates the potential for advancing local anesthesia across various medical fields, emphasizing the synergy between material science and clinical applications to improve patient care and safety.

摘要

局部麻醉在牙科实践中至关重要,特别是用于管理牙槽窝伤口的疼痛,但改善药物输送系统仍然是一个重大挑战。本研究探讨了盐酸利多卡因(LH)掺入聚电解质复合物和泊洛沙姆温敏水凝胶的理化特性,评估了其在小鼠模型中的局部麻醉效果及其作为局部麻醉剂在临床试验中的起效和作用持续时间。该温敏水凝胶在 1-3 分钟内迅速发生相转变,并表现出假塑性流动行为。其释放动力学遵循 Korsmeyer-Peppas 模型,50%的降解发生在 48 小时内。在小鼠模型中,某些温敏水凝胶表现出优越的麻醉效果,起效迅速,作用持续时间长,尾 flick 和热板模型中的热耐受能力证明了这一点。在临床试验中,负载 LH 的温敏水凝胶迅速产生麻木感,麻醉(T)开始的平均时间为 46.5±22.5 秒,有效持续时间(T)为 202.5±41.0 秒,范围为 120-240 秒,表明其具有持续释放的特性。这些结果突出了这些配方的有前途的特性:起效迅速、作用持续时间长、粘膜粘附性、生物降解性和高麻醉效果。本研究表明,这些制剂在各个医学领域中具有潜在的应用前景,强调了材料科学与临床应用之间的协同作用,以改善患者的护理和安全。

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