RESUMO
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-ß-cyclodextrin (SBEßCD). The kinetics and stoichiometry of complexation and BVC-SBEßCD association constant were evaluated by phase solubility study and Job's plot. Evidence of the BVC-SBEßCD 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-SBEßCD molar ratio, with a low association constant (13.2 M-1). SEM, DSC, and FTIR results demonstrated the host-guest interaction. The IC50% values determined in SH-SY5Y were 216 µM and 149 µM for BVC and BVC-SBEßCD, respectively (p < 0.05). There was no difference in HaCaT IC50%. In orofacial pain model, BVC-SBEßCD significantly prolonged antinociceptive effect, in about 2 h, compared to plain BVC. SBEßCD can be used as a drug delivery system for bupivacaine, whereas the complex showed long-lasting analgesic effects.