Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 10;10(12):811.
doi: 10.3390/gels10120811.

Ketoprofen Associated with Hyaluronic Acid Hydrogel for Temporomandibular Disorder Treatment: An In Vitro Study

Diego Garcia Miranda  1   2   3 , Lucas de Paula Ramos  3   4 , Nicole Fernanda Dos Santos Lopes  2 , Nicole Van Der Heijde Fernandes Silva  2 , Cristina Pacheco Soares  5 , Flavia Pires Rodrigues  6 , Vinicius de Paula Morais  7 , Thalita Sani-Taiariol  8 , Mauricio Ribeiro Baldan  8 , Luana Marotta Reis de Vasconcellos  2 , Alexandre Luiz Souto Borges  2 , Brigitte Grosgogeat  1   9   10 , Kerstin Gritsch  1   9   10
Affiliations

Ketoprofen Associated with Hyaluronic Acid Hydrogel for Temporomandibular Disorder Treatment: An In Vitro Study

Diego Garcia Miranda et al. Gels. .

Abstract

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.

Keywords: non-steroidal anti-inflammatory agents 1; osteoarthritis 3; polysaccharides 2.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
FTIR spectra of HA (line black), KET (line green), and hydrogel 3% HA associated with 1% KET (line blue). The vertically dotted black lines indicate the molecular signatures of HA present in the isolated molecule and in the gel combined with KET. The vertically dotted lines in green indicate the molecular signatures of KET present in the isolated molecule and in the gel combined with HA.
Figure 2
Figure 2
Analysis of the decomposition of masses in relation to temperature. TGA spectra of HA (line black), KET (line green), and hydrogel 3% HA associated with 1% KET (line blue).
Figure 3
Figure 3
Frequency sweep of 3% HA + 0.125% KET hydrogel non-autoclaved (A), 3% hyaluronic acid HA + 0.250% KET hydrogel non-autoclaved (B), 3% HA + 0.500% KET hydrogel non-autoclaved (C), 3% HA + 1% KET hydrogel non-autoclaved (D), 3% HA + 0.125% KET hydrogel autoclaved (E), 3% HA + 0.250% KET hydrogel autoclaved (F), 3% HA + 0.500% KET hydrogel autoclaved (G), 3% HA + 1% KET hydrogel autoclaved (H), 3% HA + 0.125% KET hydrogel autoclaved cycled (I), 3% HA + 0.250% KET hydrogel autoclaved cycled (J), 3% HA + 0.500% KET hydrogel autoclaved cycled (K), 3% HA + 1% KET hydrogel autoclaved cycled (L).
Figure 4
Figure 4
Amplitude sweep of 3% HA + 0.125% KET hydrogel non-autoclaved (A), 3% HA + 0.250% KET hydrogel non-autoclaved (B), 3% HA + 0.500% KET hydrogel non-autoclaved (C), 3% HA + 1% KET hydrogel non-autoclaved (D), 3% HA + 0.125% KET hydrogel autoclaved (E), 3% HA + 0.250% KET hydrogel autoclaved (F), 3% HA + 0.500% KET hydrogel autoclaved (G), 3% HA + 1% KET hydrogel autoclaved (H), 3% HA + 0.125% KET hydrogel autoclaved cycled (I), 3% HA + 0.250% KET hydrogel autoclaved cycled (J), 3% HA + 0.500% KET hydrogel autoclaved cycled (K), 3% HA + 1% KET hydrogel autoclaved cycled (L).
Figure 5
Figure 5
Temperature ramp of 3% HA + 0.125% KET hydrogel non-autoclaved (A), 3% HA + 0.250% KET hydrogel non-autoclaved (B), 3% HA + 0.500% KET hydrogel non-autoclaved (C), 3% HA + 1% KET hydrogel non-autoclaved (D), 3% HA + 0.125% KET hydrogel autoclaved (E), 3% HA + 0.250% KET hydrogel autoclaved (F), 3% HA + 0.500% KET hydrogel autoclaved (G), 3% HA + 1% KET hydrogel autoclaved (H), 3% HA + 0.125% KET hydrogel autoclaved cycled (I), 3% HA + 0.250% KET hydrogel autoclaved cycled (J), 3% HA + 0.500% KET hydrogel autoclaved cycled (K), 3% HA + 1% KET hydrogel autoclaved cycled (L).
Figure 6
Figure 6
Micrography of 3% HA hydrogel (A), 3% HA + 0.125% KET hydrogel (B), 3% HA + 0.250% KET hydrogel (C), 3% HA + 0.500% KET hydrogel (D), 3% HA + 1% KET hydrogel (E).
Figure 7
Figure 7
Cytocompatibility by hydrogels on mouse macrophages (RAW 264.7). p < 0.0021 (**), p < 0.0002 (***), p < 0.0001 (****).
Figure 8
Figure 8
Genotocixity assay by micronucleus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Phillips D.J., Gelb M., Brown C.R., Kinderknecht K.E., Neff P.A., Kirk W.S., Schellhas K.P., Biggs J.H., Williams B. Guide to Evaluation of Permanent Impairment of the Temporomandibular Joint. CRANIO®. 1997;15:170–176. doi: 10.1080/08869634.1997.11746009. - DOI - PubMed
    1. Valesan L.F., Da-Cas C.D., Réus J.C., Denardin A.C.S., Garanhani R.R., Bonotto D., Januzzi E., De Souza B.D.M. Prevalence of Temporomandibular Joint Disorders: A Systematic Review and Meta-Analysis. Clin. Oral Investig. 2021;25:441–453. doi: 10.1007/s00784-020-03710-w. - DOI - PubMed
    1. Wu J., Huang Z., Chen Y., Chen Y., Pan Z., Gu Y. Temporomandibular Disorders among Medical Students in China: Prevalence, Biological and Psychological Risk Factors. BMC Oral Health. 2021;21:549. doi: 10.1186/s12903-021-01916-2. - DOI - PMC - PubMed
    1. Cardoneanu A., Macovei L.A., Burlui A.M., Mihai I.R., Bratoiu I., Rezus I.I., Richter P., Tamba B.-I., Rezus E. Temporomandibular Joint Osteoarthritis: Pathogenic Mechanisms Involving the Cartilage and Subchondral Bone, and Potential Therapeutic Strategies for Joint Regeneration. Int. J. Mol. Sci. 2022;24:171. doi: 10.3390/ijms24010171. - DOI - PMC - PubMed
    1. Ibi M. Inflammation and Temporomandibular Joint Derangement. Biol. Pharm. Bull. 2019;42:538–542. doi: 10.1248/bpb.b18-00442. - DOI - PubMed