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Physical–Chemical Properties and Transfection Activity of Cationic Lipid/DNA Complexes
Authors:Maria N. Antipina Dr.  Ingo Schulze Dr.  Martin Heinze  Bodo Dobner Prof. Dr.  Andreas Langner Prof. Dr.  Gerald Brezesinski Prof. Dr.
Affiliation:1. Max Planck Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam (Germany), Fax: (+49)?331‐567‐9202;2. Institute of Materials Research and Engineering, 3 Research Link, 117602 (Singapore), Fax: (+65)?687‐275‐28;3. Institute of Pharmacy, Martin‐Luther‐University, Wolfgang‐Langenbeck‐Str. 4, 06120 Halle/S. (Germany)
Abstract:Investigation of DNA interactions with cationic lipids is of particular importance for the fabrication of biosensors and nanodevices. Furthermore, lipid/DNA complexes can be applied for direct delivery of DNA‐based biopharmaceuticals to damaged cells as non‐viral vectors. To obtain more effective and safer DNA vectors, the new cationic lipids 2‐tetradecylhexadecanoic acid‐{2‐[(2‐aminoethyl)amino]ethyl}amide (C I ) and 2‐tetradecylhexadecanoic acid‐2‐[bis(2‐aminoethyl)amino]ethylamide (C II ) were synthesized and characterized. The synthesis, physical–chemical properties and first transfection and toxicity experiments are reported. Special attention was focused on the capability of C I and C II to complex DNA at low and high subphase pH values. Langmuir monolayers at the air/water interface represent a well‐defined model system to study the lipid/DNA complexes. Interactions and ordering of DNA under Langmuir monolayers of the new cationic lipids were studied using film balance measurements, grazing incidence X‐ray diffraction (GIXD) and X‐ray reflectivity (XR). The results obtained demonstrate the ability of these cationic lipids to couple with DNA at low as well as at high pH value. Moreover, the observed DNA structuring seems not to depend on subphase pH conditions. An influence of the chemical structure of the lipid head group on the DNA binding ability was clearly observed. Both compounds show good transfection efficacy and low toxicity in the in vitro experiments indicating that lipids with such structures are promising candidates for successful gene delivery systems.
Keywords:DNA  lipids  monolayers  transfection  X‐ray scattering
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