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Evaluation of the neurotoxic effects of bupivacaine complexed on sulfobutylether-²-cyclodextrin

Grant number: 19/14941-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2020
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Luiz Eduardo Nunes Ferreira
Grantee:Julia das Neves Rodrigues Ferreira
Host Institution: Universidade Universus Veritas Guarulhos (Univeritas UNG). Guarulhos , SP, Brazil


Local anesthetics (LAs) are widely used for pain control in many clinical procedures or in another kind, and also have other therapeutic applications. Bupivacaine is a long-lasting LA with increased potency, however, it has lower solubility and higher toxicity. The complexation of LA on cyclodextrins has demonstrated reduced systemic toxicity, improvements on aqueous solubility and other biopharmaceutical properties. This study aims to prepare a bupivacaine formulation complexed in sulfobutylether-²-cyclodextrin (SBE²CD) and confirm the complex formation. Moreover, evaluate the formulation cytotoxicity in neuronal cells and compare with plain bupivacaine. The inclusion complex will be obtained by mixing bupivacaine with SBE²CD in 1:1 molar ratio. The complex formation will be confirmed by morphological analysis of the molecules using the scanning electron microscopy. Cell viability will be tested by MTT reduction assay. Neuroblastoma cells (SH-SY5Y) will be transferred to the 96-well cell culture plates at the density of 1x104 cells/well. The cells will be exposure to plain bupivacaine or bupivacaine complexed in SBE²CD at different concentrations (1 µM, 10 µM, 100 µM, 1000 µM e 5000 µM). Data will be tested for normal distribution, the equivalence of variance and submitted to Analysis of Variance with the appropriate posthoc test. The significance level will be set at 5% (±=0,05).

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