Enhanced Anti-Arthritic Activity of a Garcinol-Loaded Liposomal Hydrogelin Complete Freund’s Adjuvant-Induced Arthritic Rats

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by synovial inflammation, cartilage degradation, and bone erosion, leading to progressive joint dysfunction. Garcinol, a natural polyisoprenylated benzophenone isolated from Garcinia indica, possesses potent anti-inflammatory and antioxidant properties; however, its therapeutic application is limited by poor aqueous solubility and low bioavailability. The present study aimed to develop a garcinol-loaded liposomal hydrogel and evaluate its antiarthritic efficacy in Complete Freund’s Adjuvant (CFA)-induced arthritic rats. Objective: This study aimed to develop a nanocarrier-based topical formulation of garcinol by incorporating optimized liposomes into a hydrogel matrix and to investigate its physicochemical characteristics, in vitro release behavior, and anti-arthritic efficacy in a CFA-induced RA model. Materials and Methods: Garcinol-loaded liposomes were prepared using the thinfilm hydration method employing Phospholipon® 90H and cholesterol. The optimized liposomal formulation was incorporated into a Carbopol® 934 hydrogel matrix to obtain a topical liposomal hydrogel. The formulation was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, physicochemical properties, and in vitro drug release. Anti-arthritic activity was evaluated in CFA-induced arthritic rats by assessing paw thickness, paw edema volume, arthritis score, body weight, and histopathological alterations. Methotrexate gel (1% w/w) was used as the standard treatment. Results: The optimized garcinol-loaded liposomes exhibited a particle size of 162.4 ± 3.2 nm, PDI of 0.246 ± 0.02, zeta potential of −27.6 ± 1.5 mV, and entrapment efficiency of 81.55 ± 2.1%. The liposomal hydrogel showed suitable physicochemical characteristics with a pH of 6.82 ± 0.11 and drug content of 98.24 ± 1.36%. In vitro release studies demonstrated sustained drug release over 24 h. In vivo studies revealed that treatment with garcinol-loaded liposomal hydrogel significantly reduced paw thickness, paw edema volume, and arthritis score while improving body weight compared with the CFA control group (P < 0.001). Histopathological examination confirmed marked protection against inflammatory cell infiltration, synovial hyperplasia, cartilage destruction, and bone erosion. The anti-arthritic efficacy of the liposomal hydrogel was superior to garcinol-loaded liposomes and comparable to methotrexate gel. Discussion: The enhanced
anti-arthritic activity of the garcinol-loaded liposomal hydrogel may be attributed to the synergistic benefits of liposomal encapsulation and hydrogel-based topical delivery. Liposomes improved drug solubility and retention, whereas the hydrogel matrix provided sustained release and prolonged localization at the inflamed site. The observed reduction in inflammatory manifestations and joint damage supports the therapeutic potential of garcinol as a topical anti-arthritic agent. Conclusion: The developed garcinol-loaded liposomal hydrogel demonstrated significant anti-arthritic activity in CFA-induced arthritic rats by reducing inflammation, improving clinical symptoms, and protecting joint architecture. The formulation showed superior efficacy compared
with garcinol-loaded liposomes and comparable therapeutic performance to methotrexate gel, indicating its potential as a promising topical treatment strategy for RA.