Transcriptomic Evaluation of Hollow Microneedles-Mediated Drug Delivery for Rheumatoid Arthritis Therapy

Area of Science:

• Biomedical Engineering
• Pharmacology
• Immunology

Background:

• Rheumatoid arthritis (RA) requires long-term management, often with oral medications causing systemic side effects.
• Conventional RA treatments can lead to adverse effects due to systemic drug distribution, impacting efficacy.
• Microneedle arrays offer a minimally invasive method for localized drug delivery, bypassing systemic circulation.

Purpose of the Study:

• To evaluate the efficacy and safety of hollow microneedle array delivery of Tofacitinib and N-acetylcysteine (NAC) for rheumatoid arthritis (RA).
• To investigate the mechanistic basis of microneedle-based therapy in an RA model using multi-level analyses.
• To establish a computational and mechanistic foundation for precision targeted therapy in RA management.

Main Methods:

• Histological assessment (H&E, Safranin O-Fast Green) for inflammation and cartilage degradation.
• Micro-computed tomography (micro-CT) for evaluating bone structure alterations.
• ELISA for cytokine and oxidative stress markers, and transcriptomic profiling for gene expression analysis.

Main Results:

• Microneedle delivery of Tofacitinib and NAC demonstrated significant reduction in RA-associated inflammation and cartilage degradation.
• Molecular analyses revealed modulation of key inflammatory and oxidative stress pathways.
• Transcriptomic profiling identified specific gene expression changes and signaling pathways responsive to treatment.

Conclusions:

• Hollow microneedle arrays provide an effective and safe platform for localized delivery of RA therapeutics.
• This study validates microneedle technology for targeted treatment strategies in RA.
• The findings support microneedle-based drug delivery as a promising approach for precision medicine in chronic inflammatory conditions.