Departament of Pharmacy, Federal University of Sergipe, São Cristóvão 49100-000, SE, Brazil.
Departament of Physiology, Federal University of Sergipe, São Cristóvão 49100-000, SE, Brazil.
Molecules. 2023 May 31;28(11):4465. doi: 10.3390/molecules28114465.
Pain is one of the most prevalent and difficult to manage symptoms in cancer patients, and conventional drugs present a range of adverse reactions. The development of β-cyclodextrins (β-CD) complexes has been used to avoid physicochemical and pharmacological limitations due to the lipophilicity of compounds such as p-Cymene (PC), a monoterpene with antinociceptive effects. Our aim was to obtain, characterize, and measure the effect of the complex of p-cymene and β-cyclodextrin (PC/β-CD) in a cancer pain model. Initially, molecular docking was performed to predict the viability of complex formation. Afterward, PC/β-CD was obtained by slurry complexation, characterized by HPLC and NMR. Finally, PC/β-CD was tested in a Sarcoma 180 (S180)-induced pain model. Molecular docking indicated that the occurrence of interaction between PC and β-CD is favorable. PC/β-CD showed complexation efficiency of 82.61%, and NMR demonstrated PC complexation in the β-CD cavity. In the S180 cancer pain model, PC/β-CD significantly reduced the mechanical hyperalgesia, spontaneous nociception, and nociception induced by non-noxious palpation at the doses tested ( < 0.05) when compared to vehicle differently from free PC ( > 0.05). Therefore, the complexation of PC in β-CD was shown to improve the pharmacological effect of the drug as well as reducing the required dose.
疼痛是癌症患者最常见和最难控制的症状之一，传统药物存在一系列不良反应。β-环糊精（β-CD）复合物的开发已被用于避免由于化合物的亲脂性而产生的理化和药理学限制，例如具有镇痛作用的单萜 p-香茅烯（PC）。我们的目的是获得、表征并测量 p-香茅烯和β-环糊精（PC/β-CD）复合物在癌症疼痛模型中的作用。最初，进行了分子对接以预测复合物形成的可行性。然后，通过淤浆络合获得 PC/β-CD，并用 HPLC 和 NMR 进行表征。最后，在肉瘤 180（S180）诱导的疼痛模型中测试了 PC/β-CD。分子对接表明 PC 和β-CD 之间发生相互作用是有利的。PC/β-CD 的络合效率为 82.61%，NMR 表明 PC 络合在β-CD 腔中。在 S180 癌症疼痛模型中，与单独给予 p-香茅烯相比，PC/β-CD 显著降低了机械性痛觉过敏、自发性疼痛以及非伤害性触诊引起的疼痛（<0.05），而单独给予 p-香茅烯则没有（>0.05）。因此，PC 在β-CD 中的络合显示出改善药物的药理作用并减少所需剂量的效果。
