School of pharmacy, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Pudong New Area, Shanghai, 201203, China.
Adv Healthc Mater. 2024 Sep;13(22):e2400637. doi: 10.1002/adhm.202400637. Epub 2024 May 22.
Glucocorticoids are widely used for treating allergic rhinitis, but conventional intranasal administration encounters unfavorable nasal cilia clearance and nasal mucosal barrier. Herein, a bilateral microneedle patch is fabricated for delivering cyclodextrin-based metal-organic frameworks (CD-MOF) encapsulating dexamethasone (DXMS) and paeonol (Pae), while NaH particles are mounted on the basal part of each microneedle. By intranasal administration, the microneedles are propelled into the nasal mucosa by NaH-generated hydrogen and then swell to form a hydrogel for sustainedly releasing drugs. The DXMS/Pae combination is demonstrated to be superior to more than the twofold dose of DXMS alone for improving allergic rhinitis in rats. It involves reducing mast cell degranulation and modulating Treg/Th17 cell homeostasis, whereas inhibiting Th1 to Th2 differentiation is associated with regulating the GATA3/T-bet pathway, as well as repairing epithelial barrier function by increasing MUC1 and downregulating periostin. In addition, this delivery system modulates the lipid metabolism of the nasal mucosa. Notably, the newly designed device significantly enhances the drug's therapeutic effect, and NaH-generated hydrogen may have the potential adjunctive therapeutic effect. Collectively, such an emerging microneedle-mediated nasal drug delivery creates a new form for alleviating immune inflammation and contributes a promising solution to reduce clinical glucocorticoid abuse.
糖皮质激素广泛用于治疗过敏性鼻炎，但传统的鼻腔内给药方式存在不利的鼻纤毛清除和鼻黏膜屏障功能。本研究构建了一种双侧微针贴片，用于递送达塞米松（DXMS）和丹皮酚（Pae）包封的环糊精基金属有机骨架（CD-MOF），同时在每个微针的基部安装了氢化钠（NaH）颗粒。通过鼻腔内给药，微针在 NaH 产生的氢气的推动下进入鼻黏膜，然后膨胀形成水凝胶以持续释放药物。DXMS/Pae 联合用药在改善大鼠过敏性鼻炎方面的效果优于单独使用两倍剂量的 DXMS。其作用机制涉及减少肥大细胞脱颗粒和调节 Treg/Th17 细胞平衡，而抑制 Th1 向 Th2 的分化与调节 GATA3/T-bet 通路以及通过增加 MUC1 和下调骨桥蛋白来修复上皮屏障功能有关。此外，该递药系统还调节了鼻黏膜的脂质代谢。值得注意的是，新设计的装置显著增强了药物的治疗效果，NaH 产生的氢气可能具有潜在的辅助治疗作用。总之，这种新兴的微针介导的鼻腔药物递送为缓解免疫炎症提供了一种新形式，为减少临床糖皮质激素滥用提供了一种有前途的解决方案。
