Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma

Mingzhuo Cao,1 Mengling Zhan,1,2 Zheng Wang,1,2 Zeqian Wang,1,2 Xiu-Min Li,3 Mingsan Miao1 1Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 2College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058,...

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Autores principales:	Cao M, Zhan M, Wang Z, Li XM, Miao M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	isoliquiritigenin self-nanoemulsifying drug delivery system (smedds) ovalbumin-induced asthma eotaxin-1 increased bioavailability Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/42185a154a5f4232b3866fac6e56e4eb
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spelling	oai:doaj.org-article:42185a154a5f4232b3866fac6e56e4eb2021-12-02T13:45:28ZDevelopment of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma1178-2013https://doaj.org/article/42185a154a5f4232b3866fac6e56e4eb2020-11-01T00:00:00Zhttps://www.dovepress.com/development-of-an-orally-bioavailable-isoliquiritigenin-self-nanoemuls-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mingzhuo Cao,1 Mengling Zhan,1,2 Zheng Wang,1,2 Zeqian Wang,1,2 Xiu-Min Li,3 Mingsan Miao1 1Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 2College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 3Department of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY 10595, USACorrespondence: Xiu-Min LiDepartment of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY 10595, USAEmail XiuMin_Li@NYMC.eduMingsan MiaoAcademy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of ChinaEmail miaomingsan@126.comPurpose: Isoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability.Methods: The optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated.Results: The ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was − 12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg).Conclusion: Compared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.Keywords: isoliquiritigenin, self-nanoemulsifying drug delivery system, SMEDDS, ovalbumin-induced asthma, eotaxin-1, increased bioavailabilityCao MZhan MWang ZWang ZLi XMMiao MDove Medical Pressarticleisoliquiritigeninself-nanoemulsifying drug delivery system (smedds)ovalbumin-induced asthmaeotaxin-1increased bioavailabilityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 8945-8961 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	isoliquiritigenin self-nanoemulsifying drug delivery system (smedds) ovalbumin-induced asthma eotaxin-1 increased bioavailability Medicine (General) R5-920
spellingShingle	isoliquiritigenin self-nanoemulsifying drug delivery system (smedds) ovalbumin-induced asthma eotaxin-1 increased bioavailability Medicine (General) R5-920 Cao M Zhan M Wang Z Wang Z Li XM Miao M Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma
description	Mingzhuo Cao,1 Mengling Zhan,1,2 Zheng Wang,1,2 Zeqian Wang,1,2 Xiu-Min Li,3 Mingsan Miao1 1Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 2College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of China; 3Department of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY 10595, USACorrespondence: Xiu-Min LiDepartment of Microbiology and Immunology, and Otolaryngology, New York Medical College, Valhalla, NY 10595, USAEmail XiuMin_Li@NYMC.eduMingsan MiaoAcademy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450058, People’s Republic of ChinaEmail miaomingsan@126.comPurpose: Isoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability.Methods: The optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated.Results: The ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was − 12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg).Conclusion: Compared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.Keywords: isoliquiritigenin, self-nanoemulsifying drug delivery system, SMEDDS, ovalbumin-induced asthma, eotaxin-1, increased bioavailability
format	article
author	Cao M Zhan M Wang Z Wang Z Li XM Miao M
author_facet	Cao M Zhan M Wang Z Wang Z Li XM Miao M
author_sort	Cao M
title	Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma
title_short	Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma
title_full	Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma
title_fullStr	Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma
title_full_unstemmed	Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma
title_sort	development of an orally bioavailable isoliquiritigenin self-nanoemulsifying drug delivery system to effectively treat ovalbumin-induced asthma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/42185a154a5f4232b3866fac6e56e4eb
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Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma

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