Lamellar versus Micellar Structures—Aggregation Behavior of a Three‐Chain Cationic Lipid Designed for Nonviral Polynucleotide Transfer |
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Authors: | Dr Christian Wölk Christopher Janich Dr Dorota Pawlowska Dr Simon Drescher Dr Annette Meister Dr Gerd Hause Prof Bodo Dobner Prof Andreas Langner Prof Gerald Brezesinski |
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Institution: | 1. Martin Luther University Halle‐Wittenberg, Institute of Pharmacy, Wolfgang‐Langenbeck‐Stra?e 4, 06120 Halle (Saale) (Germany);2. Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam (Germany);3. Martin Luther University Halle‐Wittenberg, Center for Structure and Dynamics of Proteins (MZP), Weinbergweg 22, 06120 Halle (Saale) (Germany);4. Martin Luther University Halle‐Wittenberg, Biocenter, Weinbergweg 22, 06120 Halle (Saale) (Germany) |
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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. |
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Keywords: | calorimetry cationic lipids gene delivery mesophases x‐ray diffraction |
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