{"title":"Ezetimibe Alters Micelle Structure and Reduces Niemann-Pick C1-like 1-Mediated Absorption of Vitamins E and K<sub>1</sub> in CaCo-2 Cells.","authors":"Hideki Aizawa","doi":"10.1016/j.xphs.2025.103712","DOIUrl":null,"url":null,"abstract":"<p><p>Ezetimibe (EZE) is known to inhibit cholesterol absorption by targeting Niemann-Pick C1-like 1 (NPC1L1). However, its effects on the absorption of fat-soluble vitamins, such as Vitamin E and Vitamin K<sub>1</sub>, remain unclear. This study investigates how EZE impacts micellar properties and vitamin absorption. We analyzed the shape, size, diffusion rate, and zeta-potential of micelles during Vitamin E and K<sub>1</sub> absorption. Our findings demonstrate that EZE causes micelles to transition from an elliptical to a cylindrical shape, reducing vitamin absorption efficiency. EZE also impairs absorption by altering micelle composition, hindering NPC1L1 binding, and directly blocking vitamin uptake. EZE negatively affects Vitamin E and K<sub>1</sub> absorption, raising concerns about potential deficiencies with long-term use. These findings highlight the need for strategies to minimize the adverse effects of EZE in clinical practice.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103712"},"PeriodicalIF":3.7000,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xphs.2025.103712","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ezetimibe (EZE) is known to inhibit cholesterol absorption by targeting Niemann-Pick C1-like 1 (NPC1L1). However, its effects on the absorption of fat-soluble vitamins, such as Vitamin E and Vitamin K1, remain unclear. This study investigates how EZE impacts micellar properties and vitamin absorption. We analyzed the shape, size, diffusion rate, and zeta-potential of micelles during Vitamin E and K1 absorption. Our findings demonstrate that EZE causes micelles to transition from an elliptical to a cylindrical shape, reducing vitamin absorption efficiency. EZE also impairs absorption by altering micelle composition, hindering NPC1L1 binding, and directly blocking vitamin uptake. EZE negatively affects Vitamin E and K1 absorption, raising concerns about potential deficiencies with long-term use. These findings highlight the need for strategies to minimize the adverse effects of EZE in clinical practice.
期刊介绍:
The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.