Ketoprofen Associated with Hyaluronic Acid Hydrogel for Temporomandibular Disorder Treatment: An In Vitro Study
Diego Garcia Miranda,
Lucas de Paula Ramos,
Nicole Fernanda dos Santos Lopes,
Nicole Van Der Heijde Fernandes Silva,
Cristina Pacheco Soares,
Flavia Pires Rodrigues,
Vinicius de Paula Morais,
Thalita Sani-Taiariol,
Mauricio Ribeiro Baldan,
Luana Marotta Reis de Vasconcellos,
Alexandre Luiz Souto Borges,
Brigitte Grosgogeat,
Kerstin Gritsch
Affiliations
Diego Garcia Miranda
Multimaterials and Interfaces Laboratory (LMI), CNRS UMR 5615, University Claude Bernard Lyon 1, University of Lyon, 6 rue Victor Grignard, 69622 Villeurbanne, France
Lucas de Paula Ramos
Laboratory “Health Systemic Process” (P2S), UR4129, Faculty of Medicine Laennec, University Claude Bernard Lyon 1, University of Lyon, 7 rue Guillaume Paradin, 69008 Lyon, France
Nicole Fernanda dos Santos Lopes
Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University, Avenida Francisco José Longo 777, São José dos Campos 12245-000, SP, Brazil
Nicole Van Der Heijde Fernandes Silva
Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University, Avenida Francisco José Longo 777, São José dos Campos 12245-000, SP, Brazil
Cristina Pacheco Soares
Laboratory of Cell Compartement Dynamics, Research and Development Institute, Paraíba Valley University, Avenida Shishima Hifumi 2911, São José dos Campos 12244-010, SP, Brazil
Flavia Pires Rodrigues
Oral Biology Division, School of Dentistry, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9LU, UK
Vinicius de Paula Morais
Anton-Paar, Rua José de Magalhães 646, São Paulo 04026-090, SP, Brazil
Thalita Sani-Taiariol
National Space Research Institute, Avenida dos astronautas 1758, São José dos Campos 12227-010, SP, Brazil
Mauricio Ribeiro Baldan
National Space Research Institute, Avenida dos astronautas 1758, São José dos Campos 12227-010, SP, Brazil
Luana Marotta Reis de Vasconcellos
Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University, Avenida Francisco José Longo 777, São José dos Campos 12245-000, SP, Brazil
Alexandre Luiz Souto Borges
Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University, Avenida Francisco José Longo 777, São José dos Campos 12245-000, SP, Brazil
Brigitte Grosgogeat
Multimaterials and Interfaces Laboratory (LMI), CNRS UMR 5615, University Claude Bernard Lyon 1, University of Lyon, 6 rue Victor Grignard, 69622 Villeurbanne, France
Kerstin Gritsch
Multimaterials and Interfaces Laboratory (LMI), CNRS UMR 5615, University Claude Bernard Lyon 1, University of Lyon, 6 rue Victor Grignard, 69622 Villeurbanne, France
Temporomandibular disorders (TMD) are a public health problem that affects around 12% of the global population. The treatment is based on analgesics, non-steroidal anti-inflammatory, corticosteroids, anticonvulsants, or arthrocentesis associated with hyaluronic acid-based viscosupplementation. However, the use of hyaluronic acid alone in viscosupplementation does not seem to be enough to regulate the intra-articular inflammatory process. So, we propose to develop and evaluate the physicochemical and biological properties in vitro of hyaluronic acid hydrogels (HA) associated with ketoprofen (KET) as a new therapeutic treatment for TMD. The hydrogels were synthesized with 3% HA and 0.125, 0.250, 0.500, or 1% KET. Physicochemical analyses of Attenuated Total reflectance-Fourier transform infrared spectroscopy (FTIR), Thermogravimetry (TGA), Rheology by Frequency, Amplitude sweeps, temperature ramp, and scanning electron microscopy (SEM) were performed with or without sterilization and cycled. Cytocompatibility and genotoxicity (micronucleus assay) were performed in mouse macrophages (RAW 264-7) for 24 h. Results: FTIR spectrum showed characteristic absorptions of HA and KET. In the TGA, two mass loss peaks were observed, the first representing the water evaporation at 30 and 100 °C, and the second peaks between 200 and 300 °C, indicating the degradation of HA and KET. Rheology tests in the oscillatory regime classified the hydrogels as non-Newtonian fluids, time-dependent, and thixotropic. Mouse macrophages (RAW 264-7) presented viability of 83.6% for HA, 50.7% for KET, and 92.4%, 66.1%, 65.3%, and 87.7% for hydrogels, in addition to the absence of genotoxicity. Conclusions: Hyaluronic acid associated with ketoprofen shows satisfactory physicochemical and biological properties for use as viscosupplementation. As a limiting point of this study, further research is needed to evaluate the pharmacodynamic, toxicological, and pharmacokinetic characteristics of a complete organism
