The temporomandibular joint (TMJ) is a synovial joint that connects the condylar process of the mandible to the mandibular fossa and articular eminence of the temporal bone at the base of the skull, with an articular disc of connective tissue in the joint cavity, delimited by the joint capsule, and the mandibular condyle covered in fibrocartilage (Iturriaga et al., 2023). This complex structure has distinct histological zones that provide adaptability (Fan et al., 2021). Symptoms of temporomandibular disorders (TMD) include pain, joint noises, and restricted mouth opening, and can be influenced by factors such as age, sex, hormones, trauma, psychological stress, and systemic conditions, including inflammatory and degenerative diseases like osteoarthritis and rheumatoid arthritis (RA) (Covert et al., 2021).

RA is a chronic autoimmune disease that primarily affects peripheral joints such as the hands, wrists, elbows, shoulders, hips, knees, and feet, and can also involve the TMJ (Ananias et al., 2023, Figueroba et al., 2014, Radu and Bungau, 2021). TMJ involvement is clinically significant, presenting with pain, edema, functional limitation, and crepitation, and in advanced cases, malocclusion and anterior open bite. Patients frequently report preauricular pain, prolonged morning stiffness, and reduced masticatory strength (Aiello et al., 2025). Moreover, RA pharmacotherapy itself may cause adverse oral effects, such as xerostomia, reported by over half of patients, leading to additional impairment in quality of life (Schmalz et al., 2020).

Given the clinical and functional burden of RA-associated TMJ involvement, effective and well-tolerated therapeutic strategies are required. Current management of TMD ranges from non-pharmacological approaches (e.g., physiotherapy, acupuncture, occlusal splints) to pharmacological treatments, such as anti-inflammatories and muscle relaxants (Albagieh et al., 2023, Ben El Hammi et al., 2025, Mohamad et al., 2024, Ozmen and Unuvar, 2024, Romero-Reyes et al., 2025). Indomethacin, a nonsteroidal anti-inflammatory drug, is effective in controlling RA pain and inflammation (Anita et al., 2021). Additionally, omega-3 fatty acids have shown anti-inflammatory potential in chronic diseases such as RA (Dyerberg et al., 1975, Parolini, 2023). More recently, nanotechnology has emerged as a promising drug delivery strategy, as nanocapsules can be tailored to enhance drug bioavailability and therapeutic performance (Purohit et al., 2023).

Therefore, this study aims to develop and characterize indomethacin nanocapsules with an omega-3 oily core and assess their potential in treating RA, focusing on the TMJ of rats. To this end, the key inflammatory cytokines (IL-1β, IL-10, IL-6, and TNF-α) will be evaluated, providing insights into both mechanistic pathways and possible translational implications for clinical management of TMJ involvement in RA.