Development and evaluation of a microneedle–assisted transdermal delivery system for compound betamethasone in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunctio​n and immune dysregulation, which may influence topical drug penetration and therapeutic efficacy. This study evaluated a microneedle-assisted approach to enhance the cutaneous delivery of compound betamethasone in AD. Franz diffusion cell experiments demonstrated 3.29-fold and 4.67-fold increases in the 24-h cumulative permeation of betamethasone dipropionate (BDP) and betamethasone sodium phosphate (BSP), respectively, compared with passive application. In vivo fluorescence imaging showed greater penetration depth of fluorescein sodium following microneedle treatment, while histological examination revealed transient epidermal disruption. In a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model, the combined treatment was associated with reduced epidermal thickening, mast cell accumulation, and serum IgE and IL-13 levels. In a pilot split-body clinical study involving 28 participants with mild-to-moderate AD, the microneedle + compound betamethasone-treated side showed greater improvements in Scoring Atopic Dermatitis (SCORAD) intensity and numeric rating scale (NRS) pruritus scores than the contralateral microneedle + saline control side after 7 days. No serious adverse events were observed during the study period. These findings demonstrate enhanced cutaneous permeation of compound betamethasone following microneedle-assisted application and provide preliminary evidence of therapeutic activity and short-term tolerability in AD.