Development of JAK inhibitor (Tofacitinib)-loaded nanogel for periodontal repair

• Grant number: 24/06093-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): October 01, 2024
• Effective date (End): March 31, 2025
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Morgana Rodrigues Guimarães Stabili
• Grantee: Angelo Constantino Camilli
• Supervisor: Patrick Van Rijn
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: University of Groningen, Netherlands
• Associated to the scholarship: 22/09056-8 - Role of JAK inhibition in modulating periodontitis., BP.DR

Abstract

The intracellular signaling pathway Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) plays an important role in the inflammatory immune response, being responsible for the production of numerous pro-inflammatory cytokines that are correlated with inflammatory resorptive disease, such as rheumatoid arthritis and periodontitis. Preclinical and clinical studies have shown promising results in the treatment of rheumatoid arthritis, psoriasis, colitis, and osteoporosis with the JAK inhibitor (Tofacitinib). Preliminary results from our research group have also demonstrated positive outcomes with systemic administration of JAK inhibitor (oral route) in models of periodontitis in rats, preventing bone resorption and stimulating bone repair, in addition to inhibiting pro-inflammatory mediators and increasing markers of resolution. With the aim of enhancing the biological effects of the inhibitor and enabling its local application in periodontal sites, the aim of this study is to develop and characterize a system for controlled release of the JAK inhibitor, through its association with a nanogel-based drug carrier, and investigate its effects on the swelling ratio, encapsulation efficiency, drug release, and osteogenic potential in rat bone marrow mesenchymal cells (BMSC).