Ionizable lipids based on branched fatty acids - An explorative study on Langmuir monolayers.

Autor: Pawlowska D; Max Planck Institute of Colloids and Interfaces, Science Park Potsdam-Golm, Am Mühlenberg 1, 14476 Potsdam, Germany., Erdmann N; Martin Luther University (MLU) Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany., Folz M; Martin Luther University (MLU) Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany., Langner A; Martin Luther University (MLU) Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany., Dobner B; Martin Luther University (MLU) Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany., Wölk C; Leipzig University, Pharmaceutical Technology, Institute of Pharmacy, Medical Faculty, Eilenburger Strasse 15a, 04317 Leipzig, Germany. Electronic address: christian.woelk@medizin.uni-leipzig.de., Brezesinski G; Max Planck Institute of Colloids and Interfaces, Science Park Potsdam-Golm, Am Mühlenberg 1, 14476 Potsdam, Germany.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Jul; Vol. 200, pp. 114338. Date of Electronic Publication: 2024 May 23.
DOI: 10.1016/j.ejpb.2024.114338
Abstrakt: Ionizable lipids are a class of pharmaceutical excipients with a main application in lipid nanoparticles for nucleic acid delivery. New ionizable lipids are needed to tune characteristics of lipid-based nucleic acid delivery systems, e.g. stability, nucleic acid loading capacity and binding strength, as well as bio-distribution. Herein, we present the synthesis of three novel ionizable lipids as putative excipients for lipid-based nucleic acid delivery systems. Langmuir monolayer experiments with classical surface pressure/area isotherm evaluation were used to understand the self-assembly behavior of the lipids. Additional experiments with surface sensitive techniques, namely grazing incidence x-ray scattering and infrared reflection-absorption spectroscopy (IRRAS), were performed to understand structural characteristics of lipid associates. The latter technique was also used to investigate the nucleic acid binding process between DNA and the ionizable lipids. Finally, first transfection experiments with the novel lipids formulated as cationic liposomes were performed providing first efficacy data. Although the alkyl chain pattern was comparable for all three ionizable lipids, the results demonstrated that with increasing head-group size the DNA binding capacity changed and the alkyl chain fluidity was increased. The lipid with the lowest phase transition temperature and the smallest packing parameter showed the highest DNA transfer efficiency.
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 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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