Lamellar versus Micellar Structures—Aggregation Behavior of a Three‐Chain Cationic Lipid Designed for Nonviral Polynucleotide Transfer

Abstract

The aggregation behavior of a cationic lipid, N-[6-amino-1-oxo-1-(N-tetradecylamino)hexan-(2S)-2-yl]-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2,2-ditetradecylpropandiamide (DiTT4), is investigated in aqueous dispersions at different pH values (5, 7.3, and 10). An unusual aggregation behavior is observed whereby DiTT4 forms bilayer structures at pH 10 and 7.3. At pH 5, rod-like micelles are the dominant aggregate form. The thermotropic and lyotropic behavior is studied using differential scanning calorimetry, small-angle X-ray scattering, and FTIR spectroscopy. In addition, investigations at the air-water interface are performed by recording area-pressure-isotherms and infrared reflection-absorption (IRRA) spectra. Complementary dynamic light scattering experiments and transmission electron microscopy (TEM and cryoTEM) are also used. The ability of DiTT4 to complex plasmid DNA is investigated using fluorescence techniques and zeta potential measurements. Cell culture experiments demonstrate the ability of DiTT4 to enhance plasmid transfer in A549 cells.

Relationship between structure and molecular interactions in monolayers of specially designed aminolipids

“…The ability to transfect cells without co-lipids and the special aggregation feature which is characterized by a pH-dependent switch from lamellar to micellar arrangements makes it an excellent candidate for biomaterial applications. 24 The present work focusses on deciphering the correlation between the chemical structure of these aminolipids and their intermolecular interactions which dictate the structural organization of the monolayers and the properties of the cross-linked nanosheets derived thereof in the future. For this purpose, the aminolipids depicted in Fig.…”

Cross-linking reactions in Langmuir monolayers of specially designed aminolipids – a toolbox for the customized production of amphiphilic nanosheets

“…The lipids have been synthetized as previously reported with confirmed high purity (>95%). 37,38 Chloroform and methanol were of the highest purity commercially available and purchased from Sigma-Aldrich (Merck KGaA, Germany). Milli-Q Millipore water with a specific resistance of 18.2 MΩ cm was used for all measurements and aqueous sample preparation.…”

“…The lipids have been synthetized as previously reported with conrmed high purity (>95%). 37,38 Chloroform and methanol were of the highest purity commercially available and purchased from Sigma-Aldrich (Merck KGaA, Germany). Milli-Q…”

Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective

“…There is also evidence that the DiTT4 lipid by itself can self‐assemble into disk‐like nanostructures that can be useful for transfection. [ 215 ]…”

“…There is also evidence that the DiTT4 lipid by itself can self-assemble into disk-like nanostructures that can be useful for transfection. [215] In another study, bicelles composed of CFL, DOTAP, and DHPC along with ligand-modified DSPE-PEG2000 or DHPE-PEG2000 were prepared for gene delivery applications. [216] The base bicelle composition was CFL, DOTAP, and DHPC in an approximately 6:1:2 molar ratio and, in some cases, ligandmodified DSPE-PEG2000 or DHPE-PEG2000 was included too.…”