Antinociceptive effects of bupivacaine and its sulfobutylether-β-cyclodextrin inclusion complex in orofacial pain.
Juliana Souza de Freitas DominguesSilmara Martins Dias Dos SantosJulia das Neves Rodrigues FerreiraBianca Miguel MontiDarciane Favero BaggioWagner HummigErika Ivanna ArayaEneida de PaulaJuliana Geremias ChichorroLuiz Eduardo Nunes FerreiraPublished in: Naunyn-Schmiedeberg's archives of pharmacology (2022)
Bupivacaine hydrochloride (BVC) represents an option to produce long-lasting analgesia, and complexation in cyclodextrins has shown improvements in biopharmaceutical properties. This study aimed to characterize and test the cytotoxicity and antinociceptive effects of BVC complexed in sulfobutylether-β-cyclodextrin (SBEβCD). The kinetics and stoichiometry of complexation and BVC-SBEβCD association constant were evaluated by phase solubility study and Job's plot. Evidence of the BVC-SBEβCD complex formation was obtained from scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The cytotoxicity was evaluated in keratinocyte (HaCaT) and neuroblastoma (SH-SY5Y). Antinociceptive effects were registered via orofacial pain models: the formalin test, carrageenan-induced hyperalgesia, and postoperative pain (intraoral incision). The complex formation occurred at a 1:1 BVC-SBEβCD molar ratio, with a low association constant (13.2 M -1 ). SEM, DSC, and FTIR results demonstrated the host-guest interaction. The IC 50% values determined in SH-SY5Y were 216 µM and 149 µM for BVC and BVC-SBEβCD, respectively (p < 0.05). There was no difference in HaCaT IC 50% . In orofacial pain model, BVC-SBEβCD significantly prolonged antinociceptive effect, in about 2 h, compared to plain BVC. SBEβCD can be used as a drug delivery system for bupivacaine, whereas the complex showed long-lasting analgesic effects.