دورية أكاديمية
أعرض في EDS

Ionizable nanoemulsions for RNA delivery into the central nervous system - importance of diffusivity.

التفاصيل البيبلوغرافية
العنوان: Ionizable nanoemulsions for RNA delivery into the central nervous system - importance of diffusivity.
المؤلفون: Borrajo ML; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain., Quijano A; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain., Lapuhs P; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain., Rodriguez-Perez AI; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Networking Research Center of Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Anthiya S; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain., Labandeira-Garcia JL; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Networking Research Center of Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Valenzuela R; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Networking Research Center of Neurodegenerative Diseases (CIBERNED), Madrid, Spain. Electronic address: rita.valenzuela@usc.es., Alonso MJ; Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: mariaj.alonso@usc.es.
المصدر: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Aug; Vol. 372, pp. 295-303. Date of Electronic Publication: 2024 Jun 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
مواضيع طبية MeSH: Emulsions* , Transfection*/methods , Nanoparticles*/chemistry , Neurons*/metabolism , RNA*/administration & dosage, Animals ; Vitamin E/chemistry ; Vitamin E/administration & dosage ; Humans ; Polyethylene Glycols/chemistry ; Cell Survival/drug effects ; Central Nervous System/metabolism ; Lipids/chemistry ; Astrocytes/metabolism ; Microglia/metabolism ; RNA, Messenger/administration & dosage ; Gene Transfer Techniques ; Diffusion ; Green Fluorescent Proteins/genetics ; Phosphatidylethanolamines
مستخلص: Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12-200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Brain delivery; Diffusivity; Nanoemulsion; RNA therapeutics; mRNA; siRNA
المشرفين على المادة: 0 (Emulsions)
63231-63-0 (RNA)
1406-18-4 (Vitamin E)
3WJQ0SDW1A (Polyethylene Glycols)
0 (Lipids)
2462-63-7 (dioleoyl phosphatidylethanolamine)
0 (RNA, Messenger)
147336-22-9 (Green Fluorescent Proteins)
0 (Phosphatidylethanolamines)
تواريخ الأحداث: Date Created: 20240623 Date Completed: 20240727 Latest Revision: 20240728
رمز التحديث: 20240728
DOI: 10.1016/j.jconrel.2024.06.051
PMID: 38909703
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4995
DOI:10.1016/j.jconrel.2024.06.051