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.
To compare the systemic efficacy of borage oil (Borago officinalis: BO) and gromwell (Lithospermum erythrorhizon), two plant species of the Boraginaceae family, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil diet for 8 weeks. Subsequently, guinea pigs were fed diets of BO (group HBO), organic extract (group HGO), or water extract (group HGW) of gromwell for 2 weeks. In groups HGO and HGW, proliferation scores and the level of ceramides, the major lipid maintaining epidermal barrier, were similar with those in normal control group BO fed BO diet for 10 weeks. Despite accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent anti-proliferative metabolite of gamma-linolenic acid (GLA: major polyunsaturated fatty acid in BO), the reversal of epidermal hyperproliferation and the ceramide level of group HBO were less than those of groups HGO and HGW. Taken together, our data demonstrate that gromwell is more effective in reversing epidermal hyperproliferation with a marked increase in ceramides.
We studied the role of the additives trehalose and poly(vinyl pyrrolidone) in the physical and pharmacokinetic properties of peptide drug incorporated hyaluronic acid microneedles. Poly(vinyl pyrrolidone) increases the mechanical strength of microneedles and ameliorates drug bioavailability in vivo, suggesting that poly(vinyl pyrrolidone) can be a promising additive in the fabrication of peptide drug-encapsulated fully dissolving microneedles.
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