A ROS-Responsive Hydrogel Microneedle System Co-Delivering Tofacitinib and Azelaic Acid for Enhanced Targeted Therapy...

Area of Science:

• Biomaterials Science
• Dermatology
• Drug Delivery Systems

Background:

• Rosacea is a chronic inflammatory skin condition with limited treatment options due to poor drug penetration and potential side effects.
• Current therapies like topical agents and antibiotics face challenges including irritation, systemic toxicity, and antibiotic resistance.

Purpose of the Study:

• To design, fabricate, and evaluate a novel ROS-responsive hydrogel microneedle (MN) system for co-delivery of tofacitinib and azelaic acid for rosacea treatment.
• To investigate the triggered drug release mechanism in high-ROS environments and compare the efficacy and safety against conventional topical delivery.

Main Methods:

• Synthesized a ROS-responsive hydrogel (HPA) and fabricated it into microneedles (MNs) for drug co-delivery (Tofa/AZA@HPA-MNs).
• Evaluated skin penetration, retention, in vitro drug release under oxidative conditions, and cytoprotective effects.
• Assessed in vivo therapeutic efficacy in a rosacea-like inflammation model, measuring inflammation, ROS levels, and JAK/STAT pathway activation.
• Conducted safety assessments to evaluate systemic toxicity.

Main Results:

• Tofa/AZA@HPA-MNs demonstrated effective skin penetration and triggered release in oxidative conditions, protecting keratinocytes.
• In vivo studies showed superior reduction in inflammation, ROS, and JAK/STAT activation compared to conventional treatments.
• Safety assessments indicated no significant systemic toxicity, addressing concerns with JAK inhibitors.

Conclusions:

• The developed Tofa/AZA@HPA-MN platform offers a promising, safe, and effective targeted therapeutic strategy for rosacea.
• This system enables triggered drug release within inflamed skin, enhancing efficacy and minimizing systemic risks.