Synergistic transdermal antioxidant therapy with idebenone-mPDA microneedles: Implications for regenerative...

Oxidative stress can hinders tissue regeneration, thus highlighting the importance of localized antioxidant-based interventions. Herein, we engineered a synergistic skin delivery platform that combined idebenone (IDB)-loaded anti-oxidative mesoporous polydopamine nanoparticles (mPDA) with dissolving microneedles (MNs) for localized anti-oxidative stress treatment. Through a soft-template synthesis, the mPDA nanocarrier was prepared, achieving a drug loading of 5.00% ± 0.26% and encapsulation efficiency of 88.36% ± 3.85%. Based on a central composite design-response surface methodology (CCD-RSM), the PVP/PVA‑based MN was optimized with robust mechanical strength to accommodate nanoparticles for skin penetration. The platform substantially enhanced the penetration depth in the skin by formation of microchannels for deep dermal delivery. Synergistic antioxidant activity was achieved, respectively scavenging 80.96% ± 4.71% DPPH radicals and 49.89% ± 4.32% hydroxyl radicals, while also greatly reducing intracellular ROS in H₂O₂-stressed PC12 cells. Additionally, it increases the neuronal differentiation rate and neurite length to two-fold, while also promoting keratinocyte migration for wound healing. This nanocomposite MN system provides enhanced localized drug delivery, combined antioxidant action, and simulation of tissue regeneration, offering a promising strategy for treatment of oxidative stress-impaired conditions.