Soft Nanocontainers Based on Hydroxyethylated Geminis: Role of Spacer in Self-Assembling, Solubilization, and Complexation with Oligonucleotide

Abstract

Self-organization of hydroxyethylated gemini surfactants with different spacer fragments 16-s-16­(OH) (s = 4, 6, 10, and 12) was studied in single solutions and in binary surfactant-oligonucleotide systems. Despite the fact that aggregation activity and solubilization capacity of aggregates decrease with an increase in spacer length, gemini with the longer spacer demonstrate superior binding capacity toward oligonucleotide as compared to single head surfactant and gemini analogs with shorter spacers. The detailed study testified that gemini with longer spacers are characterized by a looser packing mode, a moist and more polar interior, and tend to show polymorphism. These features in combination with favorable geometry factor providing suitable orientation of components are probably responsible for the beneficial lipoplex formation in the case of longer spacers. The effectiveness of oligonucleotide-surfactant complexation changes in the same order as transfection efficacy mediated by these gemini reported earlier [Zakharova, L. et al. Colloids Surf. B, 2016, 140, 269–277], which indicates that physicochemical aspects probably play a key role upon the design of nonviral vectors and may be used for prediction of transfection efficacy mediated by amphiphilic agents.

Polymer–Colloid Complexes Based on Cationic Imidazolium Amphiphile, Polyacrylic Acid and DNA Decamer

“…Liposome preparation was carried out by the thin lipid hydration technique as follows [49][50][51]: a specific amount of DPPC (5.4 mg) was solved in 100 µL of chloroform. The solvent was removed by evaporation overnight at room temperature.…”

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

“…Cationic liposomes modified with hydroxyethylated gemini surfactant 16-6-16(OH) were designed in [43], based on fundamental data on self-assembly and functional activity of the geminis [48,49]. Liposome composition was optimized (lipid/surfactant molar ratio = 35:1), so that delicate balance was attained between colloidal stability and toxicity caused by cationic surface charge.…”

Self-Assembly of Amphiphilic Compounds as a Versatile Tool for Construction of Nanoscale Drug Carriers

“…As illustrated above, amphiphilic systems are of particular interest in biomedical applications [ 2 ], which can be supported by their use as hydrotropic additives [ 129 ], nanocontainers for poorly soluble drugs [ 130 , 131 , 132 , 133 ], antimicrobial preparations [ 134 , 135 ], complexing agents for negatively charged biomolecules such as DNA and BSA [ 136 , 137 , 138 , 139 , 140 ], etc. They have been successfully used for the fabrication of drug and gene delivery systems demonstrating numerous advantages compared to non-formulated drugs, i.e., improved bioavailability, higher stability and prolonged circulation in bioenvironment, lower side effects, etc.…”