Mechanobiologically Engineered Mimicry of Extracellular Vesicles for Improved Systemic Biodistribution and Anti-Inflammatory Treatment Efficacy in Rheumatoid Arthritis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Liposomal membrane elasticity is a controlling parameter in designing liposome-based drug delivery systems and significantly affects biodistribution and biofunctional effects. Although extensively investigated in tumor models, the impact of liposomal membrane elasticity on rheumatoid arthritis (RA) remains underexplored. RA presents unique challenges, such as tortuous blood vessels, increased permeability, and chronic inflammation, which necessitate a specialized drug delivery strategy. This study aims to address these challenges by developing an engineered mimicry of extracellular vesicles (EVs) that is based on a lipid/polymer hybrid system incorporating poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) to improve mechanical robustness and therapeutic performance.Tri-ARTEX is developed as a lipid/polymer hybrid liposome encapsulating stem cell extract (CE) and microRNA (AntagomiR155), and tuned its membrane elasticity by varying the PEO-b-PCL-b-PEO fraction. Tri-ARTEX exhibited enhanced cellular uptake in Raw 264.7 macrophages as the PEO-b-PCL-b-PEO fraction increases. However, semi-elastic Tri-ARTEX 8:2 showed distinct biodistribution profiles and therapeutic effects in a murine collagen-induced arthritis (CIA) model. Compared to its soft and rigid counterparts, semi-elastic Tri-ARTEX 8:2 improved blood circulation, targeted accumulation in

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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