Physicochemical characterization and cytotoxicity of articaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

Author(s)

Burga-Sanchez, Jonny ^[1] ; Ferreira, Luiz Eduardo Nunes ^[2] ; Volpato, Maria Cristina ^[1] ; Cabeca, Luis Fernando ^[3] ; Braga, Mario ^[4] ; Fraceto, Leonardo Fernandes ^[5] ; de Paula, Eneida ^[4] ; Groppo, Francisco Carlos ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Ave Limeira 901, BR-13414903 Piracicaba, SP - Brazil

^[2] Univ Guarulhos, Lab Inflammat & Immunol, Praca Teresa Cristina 229, BR-07023070 Guarulhos, SP - Brazil

^[3] Parana Fed Technol Univ Londrina City, Ave Pioneiros 3131, Jd Morumbi, BR-86036370 Londrina, PR - Brazil

^[4] Univ Campinas UNICAMP, Inst Biol, Dept Biochem, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[5] Sao Paulo State Univ UNESP, Lab Environm Nanotechnol, Inst Sci & Technol Sorocaba, Ave Tres Marco 511, BR-18087180 Sorocaba, SP - Brazil

• Document type: Journal article
• Source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 393, n. 7 MAY 2020.
• Web of Science Citations: 0

Abstract

Articaine (ATC) is one of the most widely used local anesthetics in dentistry. Despite its safety, local toxicity has been reported. This study aimed to develop an ATC-2- hydroxypropyl-beta-cyclodextrin inclusion complex (ATC HP beta CD) and to assess its toxicity in vitro. The inclusion complex was performed by solubilization, followed by a fluorimetric and job plot assay to determine the complex stoichiometry. Scanning electron microscopy, DOSY- 1 H-NMR, differential scanning calorimetry (DSC), and sustained release kinetics were used to confirm the inclusion complex formation. In vitro cytotoxicity was analyzed by MTT assay and immunofluorescence in HGF cells. Fluorimetric and job plot assay determined the inclusion complex stoichiometry (ATC:HP beta CD = 1:1) and complex formation time (400 min), as indicated by a strong host/guest interaction (K-a = 117.8 M - 1), complexed fraction (f = 41.4%), and different ATC and ATC HP beta CD melting points (172 degrees C e 235 degrees C, respectively). The mean of cell viability was 31.87% and 63.17% for 20-mM ATC and 20-mM ATC HP beta CD, respectively. Moreover, remarkable cell toxicity was observed with free ATC by immunofluorescence. These results indicate the ATC HP beta CD complex could be used to improve the safety of ATC. Further research are needed to establish the anesthetic safety and effectiveness in vivo . (AU)

• FAPESP's process: 15/20942-6 - Antitumor effects of plain and 2-hydroxypropyl-²-cyclodextrin lidocaine and articaine formulations on in vitro and in vivo models.
• Grantee: Maria Cristina Volpato
• Support Opportunities: Regular Research Grants