Dissolving microneedle delivery of anemoside B4: a strategy to enhance therapeutic efficacy against psoriasis.

Psoriasis, a chronic immune-mediated skin disease, lacks satisfactory treatment options due to the inherent limitations of conventional drug delivery: oral therapies often induce systemic toxicity, while topical agents fail to penetrate the thickened skin barrier. Anemoside B4 (AB4), a unique triterpenoidal saponin from Pulsatilla chinensis (content up to 9.7%), has previously shown anti-inflammatory efficacy comparable to dexamethasone. However, its unfavorable physicochemical properties severely hinder oral bioavailability and skin permeation, rendering traditional administration routes ineffective for psoriasis. To overcome these delivery failures, we developed dissolving hyaluronate sodium microneedles (AB4-MNs). The microneedles achieved a tunable drug loading up to 193.7 µg per patch with a strong linear correlation (R² = 0.9769) between the feeding ratio and encapsulated content. Upon skin insertion, the MNs dissolved rapidly (within 10 min in psoriatic skin), penetrated with 92.3% efficiency, and delivered AB4 with an approximately 10-fold higher skin retention than free drug solution. The drug diffused to a depth exceeding 240 μm, and the treatment reduced epidermal thickness by ~ 67% compared to the model group. In an IMQ-induced murine model, AB4-MNs at 4 mg/kg not only reversed psoriatic phenotypes and histopathology but also significantly suppressed key pro-inflammatory cytokines (TNF-α, IL-6, IL-17A, IL-23), with efficacy comparable to halometasone at 2.5 mg/kg and superior to oral AB4 (20 mg/kg) or topical AB4 (12 mg/kg), while exhibiting an excellent safety profile. Thus, transforming AB4 into a dissolvable microneedle system represents a targeted, safe, and highly effective therapeutic strategy for psoriasis, offering a decisive advantage over conventional routes.