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Study of the anti-inflammatory and antinociceptive effects of bupivacaine complexed in sulfobutylether-²-cyclodextrin.

Grant number: 18/14206-3
Support Opportunities:Regular Research Grants
Duration: February 01, 2019 - January 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Luiz Eduardo Nunes Ferreira
Grantee:Luiz Eduardo Nunes Ferreira
Host Institution: Universidade Universus Veritas Guarulhos (Univeritas UNG). Guarulhos , SP, Brazil
Associated researchers:Eneida de Paula ; Francisco Carlos Groppo ; Juliana Geremias Chichorro ; Marcelo Franchin ; Pedro Luiz Rosalen


Local anesthetics (LA) are widely used for pain control in many clinical procedures and other therapeutic applications. These molecules can interact with several cellular structures in different signaling pathways and may modulate the inflammatory response. However, the use of LAs is restricted due to a rapid dispersion from injected site. The complexation of LA in cyclodextrin have shown improvements in aqueous solubility, reduced systemic toxicity and other biopharmaceutical properties. This study aims to prepare a formulation of bupivacaine complexed in sulfobutylether-²-cyclodextrin (SBE²CD-bupi). Moreover, test the anti-inflammatory and antinociceptive activity of the SBE²CD-bupi formulation and compare with bupivacaine. The bupivacaine will be complexed in sulfobutylether-²-cyclodextrin (SBE²CD), the physical-chemical features and in vitro release assay will be conduct to characterize the formulation. The cytotoxicity of the molecules, the effects on the release of pro-inflammatory cytokines, chemokines and activation of NF-ºB will be evaluated in vitro. The anti-inflammatory activity of the formulations will be evaluated in vivo through paw edema assay, neutrophil migration into the peritoneal cavity and the release of cytokines, chemokines and substance P in the peritoneal lavage. The mesentery will be collected and the expression of adhesion molecules (P-selectin, ICAM-1 e VCAM-1) will be tested by Western blot. The antinociceptive effects will be evaluated in an acute orofacial pain model (formalin test and post-surgical pain) and in neuropathic pain through infraorbital nerve constriction. Data will be submitted to Analysis of Variance with the appropriate post-hoc test. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
HUMMIG, WAGNER; BAGGIO, DARCIANE FAVERO; LOPES, RAPHAEL VIEIRA; SANTOS, SILMARA MARTINS DIAS DOS; FERREIRA, LUIZ EDUARDO NUNES; CHICHORRO, JULIANA GEREMIAS. Antinociceptive effect of ultra-low dose naltrexone in a pre-clinical model of postoperative orofacial pain. Brain Research, v. 1798, p. 10-pg., . (18/14206-3)

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