Antinociceptive Effect of a p-Cymene/β-Cyclodextrin Inclusion Complex in a Murine Cancer Pain Model: Characterization Aided through a Docking Study

Autor: Guimarães, Wagner B. R. Santos, Lícia T. S. Pina, Marlange A. de Oliveira, Lucas A. B. O. Santos, Marcus V. A. Batista, Gabriela G. G. Trindade, Marcelo C. Duarte, Jackson R. G. S. Almeida, Lucindo J. Quintans-Júnior, Jullyana S. S. Quintans, Mairim R. Serafini, Henrique D. M. Coutinho, Grażyna Kowalska, Tomasz Baj, Radosław Kowalski, Adriana G.
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecules; Volume 28; Issue 11; Pages: 4465
ISSN: 1420-3049
DOI: 10.3390/molecules28114465
Popis: 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 (p < 0.05) when compared to vehicle differently from free PC (p > 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.
Databáze: OpenAIRE
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