Costunolide nanosuspension loaded in dissolvable microneedle arrays for atopic dermatitis treatment

Transdermal drug delivery systems (TDDS) have garnered increasing attention due to their potential to overcome the limitations of the traditional oral route. This study developed a novel transdermal delivery system integrating costunolide nanosuspension (COS-NS) with dissolvable microneedles (DMN) to address the poor aqueous solubility and bioavailability of COS for atopic dermatitis (AD) treatment. COS-NS was prepared via antisolvent precipitation, stabilized with PVP K30 and SDS, and freeze-dried with mannitol (COS NS-M), yielding nanoparticles (203.42 ± 1.99 nm) with enhanced solubility (388.61 ± 9.35 μg/mL) and cumulative release (93.00 ± 2.92 % over 24 h). COS NS-M was incorporated into hyaluronic acid-based DMN (COS-DMN), demonstrating robust mechanical strength (0.12 N/needle) and efficient epidermal penetration (630 µm depth, 95 % success rate in mice skin). Pharmacokinetic studies in rats revealed superior transdermal performance for COS-DMN, achieving a C_max of 26.30 ± 3.49 ng/mL and AUC_0-24h of 210.80 ± 8.15 h·ng/mL, outperforming oral administration. In the 2,4-Dinitrochlorobenzene (DNCB)-induced AD mice model, COS-DMN (less than 10 % of the oral dose) significantly reduced skin thickness, pruritus scores, and inflammatory cytokines (IgE, TNF-α, IL-13) Histological and molecular analyses confirmed attenuated epidermal hyperplasia and inflammatory infiltration. These findings highlight COS-DMN as a minimally invasive, high-efficacy platform for transdermal delivery of hydrophobic therapeutics, offering a promising strategy for AD management.