Intra-Articular Injection of Rebamipide-Loaded Nanoparticles Attenuate Disease Progression and Joint Destruction in Osteoarthritis Rat Model: A Pilot Study

Objective Rebamipide has antioxidant effects and is a drug with a local rather than systemic mechanism of action. Oxidative stress and inflammation in chondrocytes are the major factors contributing to the development and progression of osteoarthritis (OA). Since OA is mainly developed in weight bearing or overused joints, the locally sustained therapy is effective for targeting inflammatory component of OA. We investigated the effects of intra-articular injection of rebamipide loaded nanoparticles (NPs) in OA rat model. Design We fabricated rebamipide-loaded methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-PDLLA) and poly(D, L-lactide- co-glycolide) (PLGA) NPs that allow the sustained release of rebamipide. In vitro, chondrocytes from rat were used to investigate the cytotoxicity and anti-inflammatory effect of rebamipide-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into 7 groups, consisting of healthy control rats and rats injected with MIA alone or in combination with NPs, rebamipide (1 mg)/NPs, rebamipide (10 mg)/NPs, rebamipide (10 mg) solution, or oral administration. Results In vitro, rebamipide/NPs dose-dependently suppressed the mRNA levels of pro-inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, matrix metalloproteinase (MMP)-3, MMP-13, and cyclo-oxygenase-2. In vivo, the mRNA levels of pro-inflammatory components most markedly decreased in the intra-articularly injected rebamipide (10 mg)/NP group compared to other groups. Macroscopic, radiographic, and histological evaluations showed that the intra-articular injection of rebamipide/NPs inhibited cartilage degeneration more than rebamipide solution or rebamipide administration. Conclusions Using a chemically induced rat model of OA, intra-articular delivery of rebamipide was associated with decreased local and systemic inflammatory response decreased joint degradation and arthritic progression.