Modulation of Pyridinium Cationic Lipid–DNA Complex Properties by Pyridinium Gemini Surfactants and Its Impact on Lipoplex Transfection Properties

Abstract

The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact towards plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viability assays, we identified the main physicochemical parameters of the lipid bilayers, liposomes and lipoplexes that are affected by the gemini surfactant addition. We also correlated the cationic bilayer composition with the dynamics of the DNA compaction process, and with transfection efficiency, cytotoxicity and internalization mechanism of the resultant nucleic acid complexes. We found that blending of gemini surfactant into the cationic bilayers fluidized the supramolecular assemblies, reduced the amount of positive charge required to fully compact the plasmid DNA and, in certain cases, changed the internalization mechanism of the lipoplexes. Transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to transfection efficiency of corresponding binary lipoplexes, also surpassing standard transfection systems. The overall impact of gemini surfactants into the formation and dynamic of cationic bilayers was found to depend heavily on the presence of co-lipids, their nature and amount present into lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically for obtaining efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery.

Synthesis, Physicochemical Characterization, and Interaction with DNA of Long‐Alkyl‐Chain Gemini Pyridinium Surfactants

“…[45,46] The lowering of the CMC in the presence of hexadecyl chains seems less evident than in the presence of dodecyl chains. This hydrophobic effect of the spacerh as been already observed for ammonium geminis urfactants and is confirmed by the pC 20 values (see the Supporting Information), which generally becomes higher when both the alkyl chains linked to nitrogen atoms and the spacer length increase in as eries. [10] This suggests that the spacer elongation can also significantly affect the properties of surfactant-DNA lipoplexes.…”

“…[2][3][4][5][6][7][8][9][10] Owing to these properties, the interesti ng emini surfactants, particularly cationic ones, has increased recently in the field of pharmaceuticals, both as noncovalent components in carbon-nanotubebased formulations [11] and as nonviral vectors in gene therapy. [12][13][14][15][16][17][18][19][20] Gene therapy (GT) is finding more and more clinical applications for monogenic disorders, cancer, and infectious diseases. [21][22][23] The first step of GT is to compact and encapsulate the therapeutic desoxyribonucleic acid (DNA) into soft nanoparticles and to deliver it into the nucleus by means of as pecific vector.…”

“…[9] Pyridinium geminis urfactants, which are structurally different from the compounds presented here (they have as pacer that bridges the heteroaromatic nitrogen atoms), have been recently proposed in the literature for transfection purposes. [20] Results and Discussion…”

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

“…1-3 A large number of dicationic and polycationic complexing agents that effectively bind and stabilise nucleic acids and thus can be used in gene therapy 4,5 or in transfer of therapeutic drugs based on siRNA or other short nucleic acids have been described. 6,7 The search for new delivery systems is aimed at development of such compounds that would not only be effective in complexation of nucleic acids, especially siRNA (small interfering RNA), but will also show the lowest possible cytotoxicity.…”

Polyethylenimine coated plasmid DNA–surfactant complexes as potential gene delivery systems

“…The behaviour of strong DNA-cationic surfactant association has been studied extensively and is linked to some remarkable applications, such as DNA extraction and purification [7][8][9] and gene delivery systems [10][11][12][13][14]. A major current research interest in the pharmaceutical and biotechnology fields is the development of safe and efficient vehicles for controlled gene release.…”