Antinociceptive effects of bupivacaine and its sulfobutylether-β-cyclodextrin inclusion complex in orofacial pain

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-beta-cyclodextrin (SBE beta CD). The kinetics and stoichiometry of complexation and BVC-SBE beta CD association constant were evaluated by phase solubility study and Job's plot. Evidence of the BVC-SBE beta CD 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-SBE beta CD 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 mu M and 149 mu M for BVC and BVC-SBE beta CD, respectively (p < 0.05). There was no difference in HaCaT IC50%. In orofacial pain model, BVC-SBE beta CD significantly prolonged antinociceptive effect, in about 2 h, compared to plain BVC. SBE beta CD can be used as a drug delivery system for bupivacaine, whereas the complex showed long-lasting analgesic effects.

Automated summary

This study aimed to improve the biopharmaceutical properties of bupivacaine hydrochloride (BVC) by forming a complex in sulfobutylether-beta-cyclodextrin (SBE beta CD). The complex formation was confirmed through various characterization techniques, and it demonstrated long-lasting analgesic effects.