Biomimetic Platelet Membrane-Coated PLGA Nanoparticles for Enhanced Zingerone Delivery in Experimental Rheumatoid Arthritis.

Abstract

OBJECTIVE: To develop and evaluate platelet membrane-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating zingerone for targeted delivery and enhanced therapeutic efficacy against experimental rheumatoid arthritis. SIGNIFICANCE: Rheumatoid arthritis is a chronic inflammatory disorder characterized by synovial inflammation, oxidative stress, and progressive cartilage and bone destruction, resulting in pain, disability, and impaired mobility. Existing therapies often provide incomplete disease control and may cause systemic adverse effects, necessitating the development of safer and more effective targeted treatment strategies. METHODS: Zingerone-loaded PLGA nanoparticles were prepared and coated with platelet membranes to improve targeting of inflamed tissues. Physicochemical characterization included particle size, zeta potential, transmission electron microscopy, and spectroscopic analyses. Therapeutic efficacy was assessed in Freund's complete adjuvant-induced arthritic rats using clinical evaluation, cytokine quantification, antioxidant assessment, histopathology, radiography, and toxicity studies. RESULTS: Optimized ZP nanoparticles exhibited a mean hydrodynamic diameter of 134.35 ± 52.21 nm, which increased to 148.88 ± 69.35 nm following platelet membrane coating (PZP), indicating successful surface modification. Transmission electron microscopy demonstrated a spherical core-shell morphology, while spectroscopic analyses confirmed successful encapsulation without evidence of chemical incompatibility. Entrapment efficiency was 81.0 ± 1.0% for ZP and 81.7 ± 0.6% for PZP. Treatment significantly reduced paw edema (P < 0.001), arthritis scores, TNF-α, and IL-1β (P < 0.05), improved antioxidant status, preserved joint architecture, and produced no significant hepatic or renal toxicity. CONCLUSIONS: Platelet membrane-coated PLGA nanoparticles effectively enhanced zingerone delivery and anti-inflammatory activity, demonstrating considerable potential as a targeted nanotherapeutic platform for the management of rheumatoid arthritis.

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