Göntér Kitti, László Szabolcs, Tékus Valéria, Dombi Ágnes, Fábián Katalin, Pál Szilárd, Pozsgai Gábor, Botz Lajos, Wagner Ödön, Pintér Erika, Hajna Zsófia
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti str. 12, H-7624, Pécs, Hungary; HUN-REN, Chronic Pain Research Group, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Magyar Tudósok Krt. 2, Budapest, 1117, Hungary.
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti str. 12, H-7624, Pécs, Hungary; Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111, Budapest, Hungary; HUN-REN, Computation-Driven Chemistry Research Group, Műegyetem rkp. 3, H-1111, Budapest, Hungary.
Eur J Pharm Sci. 2025 Apr 1;207:107035. doi: 10.1016/j.ejps.2025.107035. Epub 2025 Feb 7.
Pain is one of the major public health burdens worldwide, however, conventional analgesics are often ineffective. Capsaicin-the active compound of Capsicum species, being responsible for their pungency-has been part of traditional medicine long ago. Capsaicin is a natural agonist of the Transient Receptor Potential Vanilloid 1 receptor-localized on capsaicin-sensitive sensory neurons and strongly involved in pain transmission-, and has been in focus of analgesic drug research for many years. In this study, we aimed to develop a sustained release transdermal patch (transdermal therapeutic system, TTS) combining the advantages of low-concentration capsaicin and diclofenac embedded in an innovative structure, as well as to perform complex preclinical investigations of its analgesic effect.
Drug delivery properties of the TTS were investigated with Franz cell and flow-through cell tests. Analgesic effect of the TTS was examined in in vivo models of acute postoperative and inflammatory, chronic neuropathic and osteoarthritic pain.
Modified silicone polymer matrix-based TTS containing low-concentration capsaicin and diclofenac has been developed, releasing both compounds according to zero-order kinetics. Moreover, capsaicin and diclofenac facilitated the liberation of each other. Combined TTS significantly reduced acute postoperative and inflammatory pain, as well as chronic neuropathic and osteoarthritic pain. Interestingly, in acute postoperative and chronic osteoarthritic pain, capsaicin prolonged and potentiated the pain-relieving effect of diclofenac.
New generation combined low-concentration capsaicin-diclofenac containing TTS can be an effective therapeutic tool in acute and chronic pain states involving neuropathic and inflammatory components.
疼痛是全球主要的公共卫生负担之一，然而传统镇痛药往往无效。辣椒素——辣椒属植物的活性成分，赋予其辛辣味——很久以前就已成为传统医学的一部分。辣椒素是瞬时受体电位香草酸亚型1受体的天然激动剂，该受体位于对辣椒素敏感的感觉神经元上，且在疼痛传递中起重要作用，多年来一直是镇痛药研究的焦点。在本研究中，我们旨在开发一种缓释透皮贴剂（透皮治疗系统，TTS），它结合了低浓度辣椒素和双氯芬酸的优点，并采用了创新结构，同时对其镇痛效果进行复杂的临床前研究。
通过Franz扩散池和流通池试验研究TTS的药物释放特性。在急性术后疼痛、炎性疼痛、慢性神经性疼痛和骨关节炎疼痛的体内模型中检测TTS的镇痛效果。
已开发出基于改性有机硅聚合物基质的TTS，其含有低浓度辣椒素和双氯芬酸，两种化合物均按零级动力学释放。此外，辣椒素和双氯芬酸相互促进释放。联合TTS显著减轻了急性术后疼痛、炎性疼痛以及慢性神经性疼痛和骨关节炎疼痛。有趣的是，在急性术后疼痛和慢性骨关节炎疼痛中，辣椒素延长并增强了双氯芬酸的镇痛效果。
新一代含低浓度辣椒素 - 双氯芬酸的联合TTS可成为治疗涉及神经性和炎性成分的急慢性疼痛状态的有效治疗工具。
