Department of Chemical Engineering, Texas Tech University, Lubbock, Texas 79409, United States.
Mol Pharm. 2020 Aug 3;17(8):3033-3042. doi: 10.1021/acs.molpharmaceut.0c00447. Epub 2020 Jul 23.
Subcutaneous allergen-specific immunotherapy (SCIT) qualifies as a promising approach for the permanent cure of IgE-mediated airway allergies, which can often manifest into allergic rhinitis and other allergic respiratory diseases. SCIT entails repeated administration of a high allergen dose into the subcutaneous (sc) region using a hypodermic needle for many (3-5) years, which is inconvenient and painful and reduces patient compliance. To overcome these limitations, we hypothesized that microneedles (MNs), which are minimally invasive and painless, could provide a novel approach for allergen desensitization by depositing the allergen into the superficial layers of the skin. To test this hypothesis, we compared MNs and SCIT for allergen desensitization in a mouse model of ovalbumin (Ova)-induced airway allergy. Mice were first made allergic to Ova and then treated with MNs coated with Ova (with or without CpG as an adjuvant) or via SCIT-Ova + alum (subcutaneous Ova + alum injections) for comparison. Treatment with coated MNs significantly induced Ova-specific serum IgG antibodies in a manner comparable to SCIT-Ova + alum-treated group. To test the efficacy against allergen challenge, treated mice were challenged with Ova via the nasal route. Coated MNs with Ova and CpG (MN-Ova + CpG) considerably suppressed the airway inflammation in allergic mice, evidenced by downregulation of proinflammatory cytokines (IL-5 and IL-13), upregulation of anti-inflammatory cytokine IL-10, and activation of Ova-specific immune response in bronchoalveolar (BAL) fluid. The therapeutic capacity of MN-based allergy treatment was further validated by the reduction in eosinophil and mast cell infiltration in the lung tissues of mice treated with MN-Ova + CpG, and low deposition of mucus inside their lung bronchioles. Overall, coated MNs ameliorated the symptoms of airway allergy in mice similar to SCIT and could provide a novel means of painless allergen-specific immunotherapy.
皮下变应原特异性免疫疗法（SCIT）有望成为 IgE 介导的气道过敏的永久治疗方法，气道过敏常表现为过敏性鼻炎和其他过敏性呼吸道疾病。SCIT 需要使用皮下注射器将高剂量过敏原多次注入皮下（sc）区域，持续 3-5 年，这种方法既不方便又痛苦，降低了患者的依从性。为了克服这些限制，我们假设微针（MNs）可以提供一种新的方法，通过将过敏原沉积到皮肤的浅层来进行过敏原脱敏，MNs 微创且无痛。为了验证这一假设，我们在卵清蛋白（Ova）诱导的气道过敏小鼠模型中比较了 MNs 和 SCIT 用于过敏原脱敏的效果。首先使小鼠对 Ova 产生过敏，然后用包被 Ova 的 MNs（有或没有 CpG 作为佐剂）或通过 SCIT-Ova+ alum 进行治疗，进行比较。用包被 MNs 进行治疗，以与 SCIT-Ova+ alum 治疗组相当的方式，显著诱导了 Ova 特异性血清 IgG 抗体。为了测试针对过敏原挑战的疗效，用 Ova 通过鼻内途径对治疗后的小鼠进行了挑战。用 Ova 和 CpG 包被的 MNs（MN-Ova + CpG）显著抑制了过敏小鼠的气道炎症，这表现在促炎细胞因子（IL-5 和 IL-13）下调、抗炎细胞因子 IL-10 上调以及在支气管肺泡（BAL）液中激活 Ova 特异性免疫反应。MN 为基础的过敏治疗的治疗能力通过 MN-Ova + CpG 治疗的小鼠肺组织中嗜酸性粒细胞和肥大细胞浸润的减少以及其肺细支气管内粘液沉积的减少得到了进一步验证。总之，包被 MNs 改善了小鼠气道过敏的症状，与 SCIT 相似，并且可以提供一种无痛的过敏原特异性免疫疗法的新方法。
