Wheat germ agglutinin modified mixed micelles overcome the dual barrier of mucus/enterocytes for effective oral absorption of shikonin and gefitinib
The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to...
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Published in | Drug delivery and translational research |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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24.04.2024
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Abstract | The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy. |
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AbstractList | The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy. |
Author | Ai, Xinyi Liu, Zhenda Yang, Jiayi Feng, Nianping Wu, Yihan Hou, Xuefeng Zhang, Di |
Author_xml | – sequence: 1 givenname: Xuefeng surname: Hou fullname: Hou, Xuefeng organization: School of Pharmacy, Wannan Medical College, Wuhu, 241002, China – sequence: 2 givenname: Xinyi surname: Ai fullname: Ai, Xinyi organization: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, NO. 1200 Cailun Road, Shanghai, 201203, China – sequence: 3 givenname: Zhenda surname: Liu fullname: Liu, Zhenda organization: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, NO. 1200 Cailun Road, Shanghai, 201203, China – sequence: 4 givenname: Jiayi surname: Yang fullname: Yang, Jiayi organization: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, NO. 1200 Cailun Road, Shanghai, 201203, China – sequence: 5 givenname: Yihan surname: Wu fullname: Wu, Yihan organization: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, NO. 1200 Cailun Road, Shanghai, 201203, China – sequence: 6 givenname: Di surname: Zhang fullname: Zhang, Di organization: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, NO. 1200 Cailun Road, Shanghai, 201203, China – sequence: 7 givenname: Nianping orcidid: 0000-0002-5303-2941 surname: Feng fullname: Feng, Nianping email: npfeng@shutcm.edu.cn organization: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, NO. 1200 Cailun Road, Shanghai, 201203, China. npfeng@shutcm.edu.cn |
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Keywords | Mixed micelles Wheat germ agglutinin Energy metabolism Oral Mucus penetration Lung cancer |
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Snippet | The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor... |
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Title | Wheat germ agglutinin modified mixed micelles overcome the dual barrier of mucus/enterocytes for effective oral absorption of shikonin and gefitinib |
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