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Epicutaneous Allergen Administration with Microneedles as a Novel Method of Immunotherapy for House Dust Mite (HDM) Allergic Rhinitis

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Abstract

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.

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Abbreviations

HDM:

house dust mite

Der p:

Dermatophagoides pteronissinus

MNs:

microneedles

EPIT:

epicutaneous immunotherapy

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Funding

This work was supported by the Gachon University research fund of 2020. (GCU-2019-0814) and grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI16C2319).

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Author notes

  1. Yu-Ji Choi and Kyeong-Ah Kim contributed equally to this work.

Authors and Affiliations

  1. Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, Republic of Korea

    Yu-Ji Choi & Jung-Hwan Park

  2. Department of Otolaryngology-Head & Neck Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea

    Kyeong-Ah Kim, Joo-Hyun Jung, Yun-Sook Choi & Seon-Tae Kim

  3. QuadMedicine R&D Centre, QuadMedicine Co., Ltd, Seongnam, Republic of Korea

    Seung-Ki Baek

Authors
  1. Yu-Ji Choi
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  2. Kyeong-Ah Kim
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  4. Yun-Sook Choi
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Correspondence to Seon-Tae Kim or Jung-Hwan Park.

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Conflict of Interest

PJH is an inventor of patents that have been licensed to companies developing microneedle-based products and he is a shareholder of companies developing microneedle-based products.

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Choi, YJ., Kim, KA., Jung, JH. et al. Epicutaneous Allergen Administration with Microneedles as a Novel Method of Immunotherapy for House Dust Mite (HDM) Allergic Rhinitis. Pharm Res 38, 1199–1207 (2021). https://doi.org/10.1007/s11095-021-03070-4

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  • DOI: https://doi.org/10.1007/s11095-021-03070-4

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