Lipoplexes of dicationic gemini surfactants with DNA: Structural features of DNA compaction and transfection efficiency.

The internal structure of DNA lipoplexes with hydroxyethylated alkylammonium gemini surfactants (GS) with high transfection activity was studied by circular dichroism. It was shown that the efficiency of transfection of HEK293T cells with the pEGFP-N1 circular plasmid was different from zero only in the region of existence of chiral supramolecular DNA-GS complexes and reaches a maximum at concentrations at which the spontaneous aggregation of components is observed.

Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations.

In this study, we report the relationship between structure, self-assembly behavior and antimicrobial activity of multicationic gemini surfactants and their successful use as stabilizers of a new liposomal formulation for transdermal drug delivery. New surfactants containing natural moiety 1,4-diazabicyclo[2.2.2]octane with four charges and two hydrophobic chains (n-Dabco-s-Dabco-n, where s = 2, 6, 12 and n = 12, 14, 16, 18) were synthesized. A linear dependence of the CMC decrease, with the increase of the number of carbon atoms in alkyl groups (slope 0.23) was shown. The aggregation numbers of n-Dabco-2-Dabco-n are smaller than 30 and they decrease with increasing alkyl chain length. This is in compliance with the larger surface area per n-Dabco-2-Dabco-n molecule. New liposomal formulations loading Rhodamine B phosphatidylcholine (with mean size about 100 nm and increased zeta potential from -7 ± 2 mV to +55 ± 2 mV) have been successfully stabilized by n-Dabco-s-Dabco-n surfactants. These formulations were designed to improve the bioavailability and skin permeation of loaded compound. The antibacterial activity of Dabco-surfactants was shown to be strongly affected by their structure (alkyl chain length and number of charged nitrogen). 12-Dabco-2-Dabco-12 was the most active (MIC = 0.48, 0.98 and 15.6 µg/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 µg/mL concentration. PC/14-Dabco-2-Dabco-14-liposomes were shown to be the best formulation, with the highest antibacterial activity against Sa (MIC = 7.8 µg‧mL-1) and lowest cytotoxicity (IC50 > 125). The modification of liposomes by Dabco-surfactants stabilizes the membrane of the vesicles, preventing the release of rhodamine B and impairing the penetration of the dye across Strat-M® membrane. Cellular uptake of rhodamine B-loaded PC/12-Dabco-2-Dabco-12-liposomes was also reported. This is the first example of cationic mixed liposomes containing Dabco-surfactants of potential interest for transdermal drug delivery.

Delivery nanosystems based on sterically hindered phenol derivatives containing a quaternary ammonium moiety: Synthesis, cholinesterase inhibition and antioxidant activity.

Multitarget ligands (MTL) based on sterically hindered phenol and containing a quaternary ammonium moiety (SHP-n-Q) were synthesized. These compounds are inhibitors of cholinesterases with antioxidant properties. The inhibitory selectivity is 10-fold potent for BChE than for AChE. IC50 of SHP-n-Q for BChE is 20 µM. SHP-n-Q and their nanosystems exhibit more pronounced antioxidant properties than the synthetic antioxidant (hindered phenol, butylated hydroxytoluene). These compounds display a low hemolytic activity against human red blood cells. The nanotechnological approach was used to increase the bioavailability of SHP-n-Q derivatives. For water soluble SHP-n-Q derivative, the self-assembled structures have a size close to 100 nm at critical association concentration (0.01 M). Mixed cationic liposomes based on l-α-phosphatidylcholine and SHP-n-Q of 100 nm diameter were prepared. The stability, encapsulation efficacy and release from liposomes of a model drug, Rhodamine B, depend on the structure of SHP-n-Q. Cationic liposomes based on l-α-phosphatidylcholine and SHP-3-Q show a good stability in time (1year) and a sustained release (>65 h). They are promising templates for the development of anti-Alzheimer MT-drug delivery systems.

Palladium 1D nanoscale aggregates on a graphite surface using CTAB hemicylindrical micelle templates.

Nanoscale palladium clusters in the form of parallel strips have been formed on the surface of graphite with the help of a surface micellar template of cetyltrimethylammonium bromide using a chemical deposition method. The repeat period of the palladium strips deposited at 25 °C is 65 nm, with a width of 40 nm and height of 2 nm. The elemental composition of the metal clusters was confirmed using X-ray fluorescence analysis and TEM-EDX. The fact that the strips are composed of metallic palladium was also confirmed by testing the membrane electrode assembly with the strips in a commercial fuel cell. Using the obtained micellar template, the radius of the curvature of the AFM probe tip was estimated with the help of a unique method. The radius is equal to 10 nm and matches the value provided by the manufacturer.

Amphiphilic macrocycles bearing biofragment: molecular design as factor controlling self-assembly.

Two novel macrocyclic 6-methyluracilic amphiphiles (uracilophanes) with four (UP1) and two (UP2) uracil moieties and ammonium groups have been synthesized. Tetracationic multi-uracilophane is composed of two macrocyclic units bridged each other with an external methylene spacer, while in the cryptand-like dicationic uracilophane pyrimidinic moieties are connected with an internal methylene spacer. This internal spacer provided a conformational rigidity to the macrocycle. The self-assembly of the uracilophanes is studied and compared with a reference dicationic uracilophane (UP3) with no spacer fragment. Compounds UP1 and UP3 are capable of aggregating, which is characterized by the analogous critical micelle concentration of 1mM, although the former has four decyl tails versus two decyl tails in UP3 molecule. NMR self-diffusion, fluorimetry and DLS techniques revealed that bimodal size distribution occurs in the UP1 solution, with small (≤2nm) and large (ca. 30-50 nm) aggregates contributed. Unexpectedly, the cryptand-like uracilophane UP2 with the same hydrophobicity as UP3 does not form aggregates. The balance of the geometry and energetic factors was analyzed and compared with those contributing to the aggregation of the reference compound UP3. It was established that it is the geometry that controls the packing of the cryptand-like uracilophanes upon aggregation, while hydrophobic effect plays a minor role. In contrast, both factors control the aggregation of oligomeric macrocycle, with energetic factor prevailing. These findings are of importance for (i) the understanding the diverse structural behavior of bioamphiphiles that have very similar chemical structure, but different conformations; and (ii) the design of amphiphiles with controlled model of self-assembly. Supramolecular systems studied can be recommended for biotechnological applications.