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

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/cm2 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.