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  Structures of malonic acid diamide/phospholipid composites and their lipoplexes

Janich, C., Taßler, S., Meister, A., Hause, g., Schafer, J., Bakowsky, U., et al. (2016). Structures of malonic acid diamide/phospholipid composites and their lipoplexes. Soft Matter, 12(27), 5854-5866. doi:10.1039/C6SM00807K.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-D9F0-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-BE06-0
Genre: Journal Article

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 Creators:
Janich, Christopher, Author
Taßler, Stephanie1, Author              
Meister, Annette, Author
Hause, gerd, Author
Schafer, Jens, Author
Bakowsky, Udo, Author
Brezesinski, Gerald1, Author              
Wölk, Christian, Author
Affiliations:
1Gerald Brezesinski, Kolloidchemie, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863500              

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 Abstract: As continuation of previous works, the self-assembly process of cationic lipid formulations in presence and absence of DNA was investigated for binary lipid mixtures suitable as polynucleotide carrier systems. The lipid blends consist of one malonic acid based-cationic lipid with varying alkyl chain pattern, called N-{6-amino-1-[N-(9Z)-octadec-9-enylamino]-1-oxohexan-(2S)-2-yl}-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2-hexadecylpropandiamide (OH4) or N-[6-amino-1-oxo-1-(N-tetradecylamino)hexan-(2S)-2-yl]-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2-hexadecylpropandiamide (TH4), and one neutral co-lipid, either 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphocholine (DOPE) or 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphoethanolamine (DPPC). Although the cationic lipids exhibit only slight differences in their structure, the DNA transfer efficiency varies drastically. Therefore, self-assembly was studied in 3D systems by small- and wide- angle x-ray scattering (SAXS and WAXS) and transmission electron microscopy (TEM) as well as in 2D systems by infrared reflexion-absorption spectroscopy (IRRAS) on Langmuir films. The investigated lipid mixtures show a quite different self-assembly in absence of DNA with varying structures from vesicles (OH4/DOPE; TH4/DOPE) and tubes (TH4/DOPE) to discoid structures (OH4/DPPC; TH4/DPPC). Twisted ribbons and sheets, which were stabilized due to hydrogen bond networks, were found in all investigated lipid mixtures in absence of DNA. The addition of DNA leads to the formation of lamellar lipoplexes for all investigated lipid compositions. The lipoplexes differ in crucial parameters like the lamellar repeat distance and the spacing between the DNA strands indicating differences in the binding strength between DNA and the lipid composition. The formation of associates with an ideal charge density might emerge as key parameter for efficient DNA transfer. Furthermore, the structures observed for the different lipid compositions in absence of DNA prepare the way for other applications beside gene therapy.

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 Dates: 2016-05-302016-07-21
 Publication Status: Published in print
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 Identifiers: DOI: 10.1039/C6SM00807K
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Title: Soft Matter
  Abbreviation : Soft Matter
Source Genre: Journal
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Publ. Info: Cambridge, UK : Royal Society of Chemistry
Pages: - Volume / Issue: 12 (27) Sequence Number: - Start / End Page: 5854 - 5866 Identifier: ISSN: 1744-683X