Development And Therapeutic Evaluation Of Carnosol-Loaded Nanoparticles Against Experimental Arthritis

Abstract

Arthritis is a chronic inflammatory disorder characterized by persistent synovial inflammation, progressive cartilage destruction, and debilitating pain. The present study investigated the therapeutic potential of carnosol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles using computational, physicochemical, and biological approaches in a complete Freund's adjuvant (CFA)-induced arthritis model. Pharmacokinetic prediction demonstrated that carnosol possesses favorable absorption and safety profiles, while molecular docking revealed strong binding affinities toward tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), indicating its potential to modulate key inflammatory pathways. The prepared nanoparticles exhibited desirable physicochemical characteristics, including a uniform particle size (142.6 nm), low polydispersity index, negative zeta potential, high encapsulation efficiency (84.37%), and satisfactory drug loading, confirming successful formulation and stability. In vivo evaluation demonstrated that carnosol-loaded PLGA nanoparticles significantly alleviated inflammatory pain and produced greater therapeutic efficacy than free carnosol. Furthermore, quantitative real-time polymerase chain reaction analysis showed marked downregulation of NF-κB and TNF-α gene expression, confirming potent anti-inflammatory activity. The enhanced therapeutic performance was attributed to improved bioavailability, sustained drug release, and efficient delivery of carnosol to inflamed tissues through PLGA nanoparticles. Collectively, these findings suggest that carnosol-loaded PLGA nanoparticles represent a promising nanotherapeutic strategy for the treatment of inflammatory arthritis and warrant further preclinical investigation to facilitate future clinical translation.