Yu-Ji Choi1, Kyeong-Ah Kim2, Joo-Hyun Jung2, Yun-Sook Choi2, Seung-Ki Baek3, Seon-Tae Kim4, Jung-Hwan Park5. 1. Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, Republic of Korea. 2. Department of Otolaryngology-Head & Neck Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea. 3. QuadMedicine R&D Centre, QuadMedicine Co., Ltd, Seongnam, Republic of Korea. 4. Department of Otolaryngology-Head & Neck Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea. rhinokim2002@hanmail.net. 5. Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, Republic of Korea. pa90201@gachon.ac.kr.
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.
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.