Study on transdermal delivery system of sulforaphane chitosan nanoparticles based on methacryloylated chitosan microneedles: application in the treatment of irritant contact dermatitis

A nano-in-microneedle system delivers sulforaphane efficiently through the skin barrier for dermatitis treatment. • Network pharmacology predicts that sulforaphane treats irritant contact dermatitis by targeting multiple inflammatory pathways. • Chitosan nanoparticles encapsulate sulforaphane with high efficiency, protecting it from degradation and enabling sustained release. • The combined microneedle patch shows superior anti-inflammatory effects in mice, outperforming conventional dexamethasone ointment. • Methacrylated chitosan microneedles create microchannels, enhancing skin retention eleven-fold. Treatment of irritant contact dermatitis (ICD) is limited by the stratum corneum barrier, which hinders drug delivery and bioavailability. Sulforaphane (SFN) offers anti-inflammatory potential but suffers from poor stability and a short half-life. To address this, we developed a chitosan methacrylate (CSMA) hydrogel microneedle (MN) patch loaded with SFN-chitosan nanoparticles (SFN-CSNPs) for enhanced transdermal delivery.Network pharmacology identified 33 potential ICD-related targets of SFN, including SRC, EGFR, and JAK2, implicating pathways such as AGE-RAGE and Relaxin signaling. SFN-CSNPs were optimized via a Box-Behnken design, yielding nanoparticles with a size of 180–220 nm, PDI < 0.3, a Zeta potential of ∼ 24 mV, and a high encapsulation efficiency (91.94 ± 1.22%). These were incorporated into CSMA MNs using micromolding. The MN arrays exhibited robust mechanical strength (1.53 N/needle), enabling effective stratum corneum penetration. In vitro, the system achieved sustained release (183.6 ± 2.1 µg/cm 2 over 60 h) and 11-fold higher skin retention than the SFN solution. It also demonstrated excellent stability, retaining > 85% drug content after 30 days at 4 °C. In an ICD mouse model, SFN-CSNPs@CSMA MNs significantly reduced erythema, edema, and epidermal thickening (45.37 ± 2.86 µm), approaching normal levels (20.03 ± 3.20 µm), and outperformed both SFN-CSNPs solution and dexamethasone ointment. This nano-MN platform effectively overcomes skin barriers, enhances drug stability, and enables localized, sustained release, offering a promising strategy for delivering unstable natural compounds such as SFN to treat inflammatory skin diseases. Download: Download high-res image (210KB) Download: Download full-size image