In vivo immunological evaluation of indomethacin and omega-3 nanocapsules for the treatment of rheumatoid arthritis in the temporomandibular joints of rats.

OBJECTIVE

This study aimed to develop and characterize indomethacin nanocapsules with an omega-3 oily core and evaluate their potential for treating rheumatoid arthritis in rats, comparing their effects to free-form administration on cytokines IL-1β, IL-10, IL-6, and TNF-α in temporomandibular joint.

DESIGN

Nanocapsules were synthesized with omega-3 as the oil phase containing indomethacin. They were characterized for mean hydrodynamic diameter, polydispersity index, zeta potential, morphology (TEM), encapsulation efficiency (HPLC), and cytotoxicity in RAW 264.7 macrophages (MTT assay). For in vivo evaluation, forty-eight adult male Wistar rats (n = 6) underwent rheumatoid arthritis induction via intradermal injection of Complete Freund's Adjuvant (CFA) and bovine type II collagen (CII) at the base of the tail. Rats were treated for 7 days by oral gavage with either nanocapsules (NC5, NC2.5), free indomethacin (IND5, IND2.5), or indomethacin combined with omega-3 (IND5 +ω3, IND2.5 +ω3). Cytokine levels in the temporomandibular joint were subsequently assessed.

RESULTS

Nanocapsules displayed a spherical, well-defined morphology with diameters < 250 nm and exhibited lower cytotoxicity in RAW 264.7 cells compared to free-form treatments. In vivo, all treated groups showed significant reductions in IL-1β, IL-6, and TNF-α compared to the CFA group, along with a significant increase in IL-10.

CONCLUSIONS

Indomethacin nanocapsules with omega-3 effectively reduced pro-inflammatory cytokines and increased anti-inflammatory IL-10, demonstrating a superior immunomodulatory profile compared to free-form treatments.