Lipid nanoparticles co-loaded with miRNA-22 and methotrexate for enhanced anti-inflammatory response in rheumatoid...

Present investigation was aimed at developing methotrexate (MTX) and miR-22 mimics-loaded lipid nanoparticles for the effective treatment of rheumatoid arthritis. The dual therapeutics loaded nanoparticles was prepared and subjected to in vitro and in vivo characterizations. The in vivo study was performed on adjuvant- induced arthritis model. The addition of IL-1β significantly decreased the expression of miR-22 levels in negative control groups, whereas miR-22 mimics treated cells showed significantly higher miR-22 expression compared to both the NC groups. MTX+miR-22 showed significantly lower cell viability compared to that of free MTX indicating a synergistic anti-inflammatory in the MH7A cells. To be specific, MTX/miR-22-loaded lipid nanoparticles (MTmiR-NP) showed the significantly lower cell viability compared to any other group indicating the potential of lipid nanoparticles. Consistently, MTmiR-NP exhibited a significantly higher cell apoptosis (~50%) compared to any other tested group further reiterating the nanoparticle-based combinational therapeutics. MTmiR-NP exhibited the significant reduction in the paw thickness and significantly lower arthritic score compared to all other groups on all time points. Present study clearly highlights the potential of lipid nanoparticles-based synergistic combination of MTX and miR-22 in achieving higher therapeutic response in rheumatoid arthritis treatment.