Efficacy of transdermal immunotherapy with biodegradable microneedle patches in a murine asthma model.
BACKGROUND
House dust mite (HDM) is a well-known cause of asthma. Allergen-specific immunotherapy (AIT) can only modify the natural course of the disease. Conventional routes of HDM AIT are subcutaneous or sublingual. Subcutaneous immunotherapy (SCIT) has a disadvantage of systemic hypersensitive reaction, and the sublingual immunotherapy has a disadvantage of local allergic reaction and low drug adherence.


OBJECTIVE
To overcome the weak points of conventional AIT, we developed a HDM loaded biodegradable microneedle patch (MNP) for transdermal immunotherapy (TDIT). We aim to demonstrate the efficacy of TDIT in murine asthma model triggered by HDM compared with conventional SCIT.


METHODS
To make HDM asthma mouse model, 5-week-old BALB/c female mice were sensitized and challenged by intranasal administration of HDM. The mice were divided into 5 groups: sham, asthma, low (10 µg) and high dose (100 µg) SCIT, and TDIT (10 µg). To make HDM loaded MNP, droplet-born air blowing method was used. Airway hyperresponsiveness and allergic inflammation markers were analysed by bronchoalveolar lavage fluid, immunohistochemistry, serum immunoglobulin (Ig) analysis, and lung cytokine assays.


RESULTS
Airway hyperresponsiveness was ameliorated by TDIT. Eosinophilic inflammation in bronchoalveolar lavage was improved without adverse reactions. Reduction of Th2 (IL-4, IL-5, and IL-13) cytokines, and HDM-specific IgE, induction of Treg (IL-10, TGF-β), Th1 (IFN-γ) cytokines were observed. Eosinophilic infiltration, goblet cell hyperplasia, and subepithelial fibrosis were also alleviated by TDIT. These changes were more significant in the TDIT group than in subcutaneous AIT group.


CONCLUSION
In conclusion, HDM loaded biodegradable TDIT is a novel treatment option to treat asthma which showed more effectiveness and may have better safety profiles than conventional SCIT.
['Park|Kyung Hee|KH|0000-0003-3605-5364', 'Oh|Eun Yi|EY|', 'Han|Heejae|H|', 'Kim|Jung Dong|JD|', 'Kim|Sung Jin|SJ|', 'Jeong|Kyoung Yong|KY|0000-0001-9887-1426', 'Kim|Ji Hye|JH|', 'Park|Chang Ook|CO|0000-0003-3856-1201', 'Kim|Sung-Ryeol|SR|0000-0001-7418-0049', 'Lee|Jae-Hyun|JH|', 'Jeong|Do Hyeon|DH|', 'Yong|Tai-Soon|TS|', 'Lee|Kwang Hoon|KH|', 'Park|Jung-Won|JW|']
D020341:Absorbable Implants D000279:Administration, Cutaneous D056151:Airway Remodeling D000818:Animals D039741:Antigens, Dermatophagoides D001249:Asthma D016535:Bronchial Hyperreactivity D016207:Cytokines D040001:Dermatophagoides farinae D003888:Desensitization, Immunologic D004195:Disease Models, Animal D005260:Female D007073:Immunoglobulin E D018836:Inflammation Mediators D008168:Lung D008807:Mice, Inbred BALB C D008904:Miniaturization D009339:Needles
microneedle asthma house dust mites mice allergen immunotherapy