Wang Zhen, Lu Xiaolei, Wu Lingzhi, Jiang Xin, Wang Wei, Wang Yahua
Department of Pharmacy, Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, 314000, China.
College of Materials and Textile Engineering, Jiaxing University, Jiaxing 314001, China.
Theranostics. 2025 Jul 24;15(16):8096-8116. doi: 10.7150/thno.114152. eCollection 2025.
The cutaneous route exploits the immunocompetence of the skin, making it a favourable route for allergen-specific immunotherapy (AIT), but there must be a balance between minimal skin disruption and precise allergen delivery. Thus, we propose the use of powder-laden microneedles (pMNs) for the sustained epidermal delivery of powdery hypoallergens and immunomodulators. In this study, targeted hypoallergenic derivatives, namely, mannan-ovalbumin (mOVA) conjugates, were synthesized in a single-step process. For minimally invasive self-administration into the skin, pMNs were constructed using highly biocompatible silk fibroin (SF) with a cavity in the basal portion of each needle, which was filled with lyophilized mOVA and resiquimod powders (mOVA/R848 pMN). The resulting mOVA/R848 pMN arrays were thoroughly examined for their physical morphology, mechanical property, accumulation ability, and immune profile. The deposition of powdery mOVA and R848 improved uptake by skin dendritic cells (DCs) and stimulated the immune system more than 10 d after application. On the basis of these features, mOVA/R848 pMN arrays increased the induction of protective immune mechanisms to suppress Th2 immunity, including the Treg/Th1 bias, as well as the production of anti-inflammatory cytokines and neutralizing antibodies in an asthmatic mouse model. Compared with traditional subcutaneous immunotherapy (SCIT), a total dose of only 75 μg of OVA over three treatments was sufficient to restore immune balance and alleviate allergic symptoms during allergen exposure, highlighting the dose-sparing and frequency-sparing potential of mOVA/R848 pMN. Optimal mOVA/R848 pMN arrays represent a new therapeutic strategy for allergy treatment with convenient administration and satisfactory outcomes.
经皮途径利用皮肤的免疫活性，使其成为变应原特异性免疫疗法（AIT）的有利途径，但在最小程度的皮肤损伤与精确的变应原递送之间必须保持平衡。因此，我们提议使用载粉微针（pMNs）来实现粉末状低变应原和免疫调节剂的持续经表皮递送。在本研究中，通过一步法合成了靶向低变应原衍生物，即甘露聚糖-卵清蛋白（mOVA）缀合物。为了实现对皮肤的微创自我给药，使用具有高度生物相容性的丝素蛋白（SF）构建pMNs，每根针的基部有一个腔，腔内填充有冻干的mOVA和瑞喹莫德粉末（mOVA/R848 pMN）。对所得的mOVA/R848 pMN阵列进行了全面的物理形态、机械性能、蓄积能力和免疫特性检查。粉末状mOVA和R848的沉积改善了皮肤树突状细胞（DCs）的摄取，并在应用后10多天对免疫系统产生了更强的刺激。基于这些特性，mOVA/R848 pMN阵列增强了保护性免疫机制的诱导，以抑制Th2免疫，包括Treg/Th1偏向，以及在哮喘小鼠模型中抗炎细胞因子和中和抗体的产生。与传统的皮下免疫疗法（SCIT）相比，在三次治疗中仅75μg的OVA总剂量就足以恢复免疫平衡并减轻变应原暴露期间的过敏症状，突出了mOVA/R848 pMN的剂量节省和频率节省潜力。最佳的mOVA/R848 pMN阵列代表了一种方便给药且效果令人满意的变应性疾病治疗新策略。
