An inflammation-responsive double-layer microneedle patch for recurrent atopic dermatitis therapy

Abstract

Seeking a potent therapeutic strategy for alleviating atopic dermatitis (AD) attack and preventing its recurrence is highly desired but remains challenging in clinical practice. Here, we propose an inflammation-responsive double-layer microneedle (IDMN) patch in situ delivering VD₃ for recurrent AD therapy. IDMN comprises the backing layer part and the double-layer microneedle part, in which the inner layer is gelatin methacryloyl (GelMA) loaded with VD₃ while the outer layer is composed of hyaluronic acid (HA). Introduction of the HA backing layer and outer layer around the GelMA tips can not only provide sufficient mechanical strength to penetrate into hardened AD skin with minimal invasiveness, but also exert a strong moisturizing effect after being rapidly dissolved. The inner layer of GelMA is degraded by the matrix metalloproteinase (MMP) in a dose dependent manner, which is secreted according to the disease progression of AD. The responsive degradation of GelMA tips result in corresponding release of VD₃ to treat AD, triggering negative feedback against GelMA degradation. The IDMN administration on AD-bearing mice reveals efficient "curing" performances (including suppress erythema, scaling and lichenification, reduce epidermal thickness, inhibit mast cells infiltration, and down-regulate inflammatory factor secretion), which are basically realized through synergistic effect of the released VD₃ and the dissolved HA molecules. Importantly, the residual tips of IDMN with VD₃ are retained in the skin after the first AD relief, showing promising "warning" ability to inhibit the recurrence of AD. Hence, the developed IDMN patch is expected to be one of the excellent candidates for AD therapy and other relapsing diseases in clinical fields.

Keywords: Atopic dermatitis; Double-layer; Inflammation-responsive; Microneedle; Recurrence prevention.