دورية أكاديمية
Design and development of novel self-assembled catechol-modified bile acid conjugates as pH-responsive apical sodium-dependent bile acid transporter targeting nanoparticles.
| العنوان: | Design and development of novel self-assembled catechol-modified bile acid conjugates as pH-responsive apical sodium-dependent bile acid transporter targeting nanoparticles. |
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| المؤلفون: | Lee DN; BK21 Program, Department of Applied Life Science, Konkuk University, Chungju, 27478, Republic of Korea., Yang SB; BK21 Program, Department of Applied Life Science, Konkuk University, Chungju, 27478, Republic of Korea., Kweon S; Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea; College of Pharmacy, Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea., Lee JH; BK21 Program, Department of Applied Life Science, Konkuk University, Chungju, 27478, Republic of Korea., Lee KJ; BK21 Program, Department of Applied Life Science, Konkuk University, Chungju, 27478, Republic of Korea., Ryu Y; Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju, 27478, Republic of Korea., Shin DW; College of Biomedical and Health Science, Konkuk University, Chungju, 27478, Republic of Korea., Kim YJ; Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju, 27478, Republic of Korea., Lee YK; Department of Green Bio Engineering, Graduate School, Korea National University of Transportation, Chungju, 27469, Republic of Korea. Electronic address: leeyk@ut.ac.kr., Park J; BK21 Program, Department of Applied Life Science, Konkuk University, Chungju, 27478, Republic of Korea; Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju, 27478, Republic of Korea. Electronic address: pkjhdn@kku.ac.kr. |
| المصدر: | Biomaterials [Biomaterials] 2024 Jul; Vol. 308, pp. 122539. Date of Electronic Publication: 2024 Mar 24. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <1995-> : Amsterdam : Elsevier Science Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980- |
| مواضيع طبية MeSH: | Catechols*/chemistry , Catechols*/metabolism , Bile Acids and Salts*/metabolism , Bile Acids and Salts*/chemistry , Organic Anion Transporters, Sodium-Dependent*/metabolism , Nanoparticles*/chemistry, Animals ; Hydrogen-Ion Concentration ; Mice ; Humans ; Symporters/metabolism ; Male ; Mice, Inbred C57BL |
| مستخلص: | Catechol-based biomaterials demonstrate biocompatibility, making them suitable for a wide range of therapeutic applications when integrated into various molecular frameworks. However, the development of orally available catechol-based biomaterials has been hindered by significant pH variations and complex interactions in the gastrointestinal (GI) tract. In this study, we introduce a novel catechol-modified bile acid (CMBA), which is synthesized by anchoring the FDA-approved drug, ursodeoxycholic acid to the neurotransmitter dopamine. This modification could form a new apical sodium-dependent bile acid transporter (ASBT) inhibitor (ASBTi) due to the bile acid moiety. The computational analysis using the TRAnsient Pockets in Proteins (TRAPP) module, coupled with MD simulations, revealed that CMBA exhibits a strong binding affinity at residues 51-55 of ASBT with a low inhibitory constant (Ki) value. Notably, in slightly alkaline biological conditions, CMBA molecules self-assemble into carrier-free nanoparticles with an average size of 240.2 ± 44.2 nm, while maintaining their ability to bind with ASBT. When administered orally, CMBA accumulates in the ileum and liver over 24 h, exhibiting significant therapeutic effects on bile acid (BA) metabolism in a high-fat diet (HFD)-fed mouse model. This study underscores the therapeutic potential of the newly developed catechol-based, pH-responsive ASBT-inhibiting nanoparticles presenting a promising avenue for advancing therapy. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ASBT; Bile acid; Catechol; Dopamine; Nanomedicine; Self-assembly |
| المشرفين على المادة: | 0 (Catechols) 0 (Bile Acids and Salts) 0 (Organic Anion Transporters, Sodium-Dependent) 145420-23-1 (sodium-bile acid cotransporter) LF3AJ089DQ (catechol) 0 (Symporters) |
| تواريخ الأحداث: | Date Created: 20240329 Date Completed: 20240501 Latest Revision: 20240506 |
| رمز التحديث: | 20240506 |
| DOI: | 10.1016/j.biomaterials.2024.122539 |
| PMID: | 38552366 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1878-5905 |
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| DOI: | 10.1016/j.biomaterials.2024.122539 |