Comparison of ionizable lipids for lipid nanoparticle mediated DNA delivery.

Autor: Lotter C; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland., Kuzucu EÜ; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland., Casper J; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland., Alter CL; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland; Swiss Nanoscience Institute, University of Basel, CH-4056 Basel, Switzerland., Puligilla RD; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland., Detampel P; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland., Lopez JS; Instituto Investigación Sanitaria Fundación Jiménez Díaz, ES-28015 Madrid, Spain., Ham AS; Biozentrum, University of Basel, CH-4056 Basel, Switzerland., Huwyler J; Pharmazentrum, Division of Pharmaceutical Technology, University of Basel, CH-4056 Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2024 Dec 01; Vol. 203, pp. 106898. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1016/j.ejps.2024.106898
Abstrakt: Lipid nanoparticles (LNPs) are successfully used for RNA-based gene delivery. In the context of gene replacement therapies, however, delivery of DNA expression plasmids using LNPs as a non-viral vector could be a promising strategy for the induction of longer-lasting effects. Therefore, DNA expression plasmids (3 to 4 kbp) coding for fluorescent markers or luciferase were combined with LNPs. Different clinically used ionizable lipids (DLin-MC3-DMA, SM-102, and ALC-0315) were tested to compare their influence on DNA plasmid delivery. DNA-LNPs were characterized with respect to their colloidal properties (size, polydispersity, ζ-potential, morphology), in vitro performance (cellular uptake, DNA delivery, and gene expression), and in vivo characteristics (biodistribution and luciferase gene expression). At an optimized N/P ratio of 6, spherical, small and monodisperse particles with anionic ζ-potential were obtained. Efficient transgene expression was achieved with a minimum amount of 1 pg DNA per initially plated cells. Zebrafish studies allowed selection of DNA-LNPs, which demonstrated prolonged blood circulation, avoidance of macrophage clearance, and vascular extravasation. Our comparative study demonstrates a high impact of the ionizable lipid type on DNA-LNP performance. Superior transfection efficiency of DNA-LNPs containing the ionizable lipid ALC-0315 was confirmed in wildtype mice.
Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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