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Papers of the Week

Papers: 30 Jul 2022 - 5 Aug 2022

Animal Studies

2022 Aug 01

Naunyn Schmiedebergs Arch Pharmacol

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


de Freitas Domingues J S, Dos Santos S M D, das Neves Rodrigues Ferreira J, Monti B M, Baggio D F, Hummig W, IvannaAraya E, Paula E D, Chichorro J G, Nunes Ferreira L E
Naunyn Schmiedebergs Arch Pharmacol. 2022 Aug 01.
PMID: 35909169.


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). SEM, DSC, and FTIR results demonstrated the host-guest interaction. The IC 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. 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.