Glycyrrhetinic Acid-Loaded Poly-γ-glutamic Acid Microneedles for Treatment of Atopic Dermatitis

Vollständiger Abstract

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Background: Topical treatment of atopic dermatitis (AD) is hindered by the skin’s stratum corneum barrier. This study developed glycyrrhetinic acid (GA)-loaded poly-γ-glutamic acid (γ-PGA) dissolving microneedles (γ-PGA-GA MN) to overcome this barrier, enabling efficient transdermal delivery and enhanced anti-inflammatory efficacy. Methods: Dissolving microneedles (MNs) were fabricated via centrifugation-assisted molding. The physicochemical properties and mechanical strength of the samples were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and uniaxial compression tests. In vivo therapeutic efficacy was evaluated in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model using female BALB/c mice aged 6–8 weeks. Therapeutic outcomes were assessed through dermatitis scores, scratching frequency, and spleen indices. Histopathology, mast cell infiltration, and IgE/IL-4 levels were analyzed by hematoxylin and eosin (H&E) staining, toluidine blue staining, and enzyme-linked immunosorbent assay (ELISA), respectively. Results: Characterization revealed strong hydrogen bonding and reduced crystallinity of GA in the matrix. The MN exhibited robust mechanical strength for effective skin penetration. In vivo results showed that γ-PGA-GA MN significantly alleviated erythema and edema, with scores markedly lower than other groups. Compared to the AD model, MN treatment resulted in a 77.7% reduction in epidermal thickness and a 39.4% decrease in mast cell accumulation. Furthermore, serum IgE and skin IL-4 levels were significantly downregulated, splenomegaly was mitigated, and systemic inflammatory blood markers were normalized. Conclusions: In this study, γ-PGA-GA dissolving microneedles with excellent mechanical properties and biocompatibility were successfully developed. By enhancing drug bioavailability and leveraging the intrinsic immunomodulatory effect of the γ-PGA matrix, the MN significantly improved the therapeutic efficacy for AD, representing a highly efficient and minimally invasive transdermal strategy for the clinical management of AD.