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In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also evaluated. Combined surfactants and co-surfactants were screened, and the optimal formulation of ILQ-SNEDDS was determined according to droplet size, droplet dispersity index (DDI), and drug loading. The formulation was composed of ethyl oleate (oil phase), Tween 80 &amp; Cremophor EL (surfactant, 7:3), and PEG 400 &amp; 1,2-propylene glycol (cosurfactant, 1:1), with a mass ratio of 3:6:1. Its physicochemical properties, including drug loading, droplets\u2019 size, Zeta potential, appearance, and Fourier transform infrared (FTIR) spectroscopy, were characterized. In vitro release profile, in situ intestinal absorption, and in vivo pharmacokinetics were applied to confirm the improvement of oral ILQ bioavailability by NEDDS. Finally, the efficacy of ILQ-SNEDDS in the treatment of food allergy-induced eosinophilic esophagitis (EOE) was further evaluated. When the ILQ drug loading was 77.9 mg\/g, ILQ-SNEDDS could self-assemble into sub-spherical uniform droplets with an average size of about 33.4 \u00b1 2.46 nm (PDI about 0.10 \u00b1 0.05) and a Zeta potential of approximately \u221210.05 \u00b1 3.23 mV. In situ intestinal absorption showed that optimized SNEDDS significantly increased the apparent permeability coefficient of ILQ by 1.69 times, and the pharmacokinetic parameters also confirmed that SNEDDS sharply increased the max plasma concentration and bioavailability of ILQ by 3.47 and 2.02 times, respectively. ILQ-SNEDDS also significantly improved the apparent signs, allergic index, hypothermia and body weight of EoE model mice. ILQ-SNEDDS treatment significantly reduced the levels of inflammatory cytokines, such as TNF-\u03b1, IL-4, and IL-5, and the level of PPE-s-IgE in serum, and significantly inhibited the expression of TGF-\u03b21 in esophageal tissue. SNEDDS significantly improved the solubility and bioavailability of ILQ. Additionally, ILQ-SNEDDS treatment attenuated symptomatology of EoE model mice, which was associated with inhibiting the production of TH2 inflammatory cytokines and PPE-s-IgE and the expression of TGF-\u03b21. The above results shows that ILQ-SNEDDS has great potential as a good candidate for the treatment of eosinophilic esophagitis.<\/jats:p>","DOI":"10.3390\/ph15121587","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T06:58:29Z","timestamp":1671433109000},"page":"1587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Development of an Oral Isoliquiritigenin Self-Nano-Emulsifying Drug Delivery System (ILQ-SNEDDS) for Effective Treatment of Eosinophilic Esophagitis Induced by Food Allergy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-6299","authenticated-orcid":false,"given":"Mingzhuo","family":"Cao","sequence":"first","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, China"},{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, China"},{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyun","family":"Jing","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Geng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsan","family":"Miao","sequence":"additional","affiliation":[{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, and Department of Otolaryngology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/s41598-018-19309-x","article-title":"Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis like disease through modulating PAR-2 transduction pathway in peanut sensitized mice","volume":"8","author":"Lianto","year":"2018","journal-title":"Sci. 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