ROS-Responsive Microneedle Patch for Targeted Delivery of Cryptotanshinone in Synergistic Antibacterial and Antioxidant Therapy of Infected Wounds

Abstract Chronic infected wounds remain a major clinical challenge due to persistent oxidative stress, bacterial colonization, and delayed tissue regeneration. To address these issues, we developed a reactive oxygen species (ROS)-responsive microneedle (MN) patch incorporating cryptotanshinone (CPT), a traditional Chinese medicine monomer with proven antioxidant and antibacterial properties. The microneedles were fabricated using a mold-casting technique based on a hydrogel matrix formed by tannic acid–quaternized chitosan (TA-QCTS), which endowed the patch with ROS-triggered degradation and controlled drug release. The resulting CPT-loaded microneedles exhibited uniform morphology, adequate mechanical strength (> 0.25 N/needle), and reliable skin insertion capacity. In vitro release assays confirmed efficient CPT encapsulation and sustained release under oxidative conditions mimicking the wound microenvironment. Antibacterial tests demonstrated potent inhibition against Staphylococcus aureus, Escherichia coli, and Streptococcus pyogenes. Moreover, the CPT-MN system effectively suppressed intracellular ROS, reduced pro-inflammatory cytokines (TNF-α, IL-6), upregulated anti-inflammatory IL-10, and promoted fibroblast proliferation and migration. Overall, this ROS-responsive microneedle platform combines smart drug delivery with bioactive phytochemicals, offering a promising strategy for localized treatment of chronic infected wounds.