Purpose

Epicutaneous immunotherapy (EPIT) is being studied as a method for treating allergic rhinitis because of skin immunology, user convenience and enhanced patient compliance. However, the use of EPIT is limited because of the very low skin permeability of the allergen. In this study, the limitations of EPIT were overcome by using sophisticated delivery with microneedles. The immunological efficacy of this method was studied in a murine model of house dust mite (HDM) allergic rhinitis.

Methods

The length of the microneedles was 400 μm, and the coating formulation containing HDM was locally distributed near the end of the microneedle tips. The change of distribution of FITC-dextran in porcine skin in vitro was observed over time using a confocal microscope. The effect of immunotherapy in the allergic rhinitis model, sensitized by HDM-coated microneedles (HDM MNs), was observed according to the amount of HDM applied.

Results

The microneedles delivered the coating formulation with precision into the porcine skin layer, and the coated formulation on the microneedles was all dissolved in the porcine skin in vitro within 20 min of administration and then gradually diffused into the skin layer. When HDM MNs were administered to mice, a 0.1-μg dose of HDM provided the most effective immunization, and improved efficacy was shown between 0.1- and 0.5- μg doses of HDM.

Conclusions

Effective immunotherapy can be achieved by precision delivery of the allergen into the skin layer, and microneedles can provide effective immunological therapy by delivering the appropriate amount of allergen.

中文翻译：

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使用微针进行表皮过敏原给药作为屋尘螨 (HDM) 过敏性鼻炎的一种新型免疫疗法

目的

由于皮肤免疫学、用户便利性和增强的患者依从性，表皮免疫疗法 (EPIT) 正在被研究作为治疗过敏性鼻炎的方法。然而，EPIT 的使用受到限制，因为过敏原的皮肤渗透性非常低。在这项研究中，EPIT 的局限性通过使用复杂的微针递送而被克服。在屋尘螨 (HDM) 过敏性鼻炎的小鼠模型中研究了该方法的免疫学功效。

方法

微针的长度为 400 μm，含有 HDM 的涂层制剂局部分布在微针尖端附近。使用共聚焦显微镜观察FITC-葡聚糖在体外猪皮肤中的分布随时间的变化。根据应用的 HDM 量观察免疫疗法在过敏性鼻炎模型中的效果，该模型由 HDM 涂层微针 (HDM MNs) 致敏。

结果

微针将包衣制剂精准地送入猪皮层，微针上的包衣制剂在给药后20分钟内全部溶解在猪皮中，然后逐渐扩散到皮层中。当向小鼠施用 HDM MN 时，0.1-μg 剂量的 HDM 提供了最有效的免疫，并且在 0.1- 和 0.5-μg 剂量的 HDM 之间显示出提高的功效。

结论

通过将过敏原精确递送到皮肤层中可以实现有效的免疫治疗，而微针可以通过递送适量的过敏原来提供有效的免疫治疗。