Thermosensitive smart hydrogel of PEITC ameliorates the therapeutic efficacy in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune condition that accompanies chronic inflammation of joints with limited therapeutic options. Phenethyl isothiocyanate (PEITC), a bioactive phytochemical, exerts its chemopreventive, anti-oxidant, and anti-inflammatory activity via the Nrf-2 pathway. However, limited water solubility, short half-life, and instability are reasons for the low bioavailability of PEITC that hampers clinical application. From studies in healthy rats, the performance of PEITC-loaded chitosan/pluronic F-127 smart hydrogel (PH) as a thermosensitive injectable demonstrated adequate thermosensitivity (gel formation), injectability (ease of administration), biocompatibility (with prolonged contact), pharmacokinetics (sustained drug release), and biosafety (nontoxic to major organs). In the adjuvant-induced arthritis (AIA) rat model, PEITC-hydrogel (PH50) injected into the knee joint lowered RA-related symptoms significantly (paw edema and arthritis score). Further, a marked reduction in bone erosion and inflammation-specific biomarkers was observed. Finally, this study demonstrates a smart injectable hydrogel optimally loaded with PEITC which is safe, biocompatible and exhibits significant therapeutic efficacy in RA conditions.