Nonviral gene delivery: gemini bispyridinium surfactant-based DNA nanoparticles.

The interaction with a model membrane, the formation of DNA nanoparticles, and the transfection ability of a homologous series of bispyridinium dihexadecyl cationic gemini surfactants, differing in the length of the alkyl spacer bridging the two pyridinium polar heads in the 1 and 1' positions (P16-n with n = 3, 4, 8, 12), have been studied by means of differential scanning calorimetry (DSC), atomic force microscopy, electrophoresis mobility shift assay, and transient transfection assay measurements. The results presented here show that their performance in gene delivery is strictly related to their structure in solution. For the first time the different transfection activities of the compounds can be explained by referring to their thermodynamic properties in solution, previously studied.

New gluconamide-type cationic surfactants: Interactions with DNA and lipid membranes.

New linear cationic surfactants - 2-(alkyldimethylammonio)ethylgluconamide bromides, denoted as CnGAB, n=10, 12, 14 and 16 - were synthesized from natural resources and characterized with respect to their potential as gene-delivery agents in gene therapy applications. Interactions with plasmid DNA and with model membranes were studied both experimentally and theoretically. The compounds with n=12, 14 and 16 show exponentially increasing ability to fully condense DNA.

Prediction of critical micelle concentration of nonionic surfactants by a quantitative structure - property relationship.

A quantitative structure - property relationship (QSPR) was used to predict the critical micelle concentration (cmc) of nonionic surfactants. The relation was developed for a diverse set of 23 nonionic surfactants (r = 0.99, F-test = 1042.

Aggregation studies of n-alkanoyl-N-methyllactitolamine surfactants.

The micellization processes of n-alkanoyl-N-methyllactitolamines (CnMeLA) were studied by means of isothermal titration calorimetry (ITC) and compared with those of decanoyl-N-methyl glucamide (MEGA-10). The critical micelle concentrations (cmc), the enthalpies (deltaH(m)) and the entropies (deltaS(m)0) of micellization as well as the contributions of the head groups to the Gibbs free energies (deltaG(m)0 (hy)) were calculated. The molecular modeling studies including the conformational analysis and calculations of some molecular descriptors related to hydrophilic and hydrophobic interactions were done to elucidate the experimental results at the atomic level.

Thermodynamics and biological properties of the aqueous solutions of new glucocationic surfactants.

Thermodynamic properties of aqueous solutions of newly synthesized compounds, namely, N-[2-(beta-D-glucopyranosyl)ethyl]-N,N-dimethyl-N-alkylammonium bromides with hydrophobic tails of 12 (C12DGCB) and 16 (C16DGCB) carbon atoms, determined as a function of concentration by means of direct methods, are reported here. Dilution enthalpies, densities, and sound velocities were measured at 298 K, allowing for the determination of apparent and partial molar enthalpies, volumes, and compressibilities. Changes in thermodynamic quantities upon micellization were derived using a pseudophase-transition approach.

The influence of cholesterol on the interaction between N-dodecyl-N,N-dimethyl-N-benzylammonium halides and phosphatidylcholine bilayers.

Effects of N-dodecyl-N,N-dimethyl-N-benzylammonium halides (DBeAX) on thermotropic phase behavior of phosphatidylcholine/cholesterol bilayers as well as on 1H NMR spectra were studied. The surfactants were added either to the water phase or directly to the lipid phase (a mixed film was formed). The benzyl group, opposite to liposomes without cholesterol, is not incorporated into the bilayer in the gel state but only in the liquid state.

Biologically active bisquaternary ammonium chlorides: physico-chemical properties of long chain amphiphiles and their evaluation as non-viral vectors for gene delivery.

The biological properties of bisquaternary ammonium salts, which are derivatives of N,N-bisdimethyl-1,2-ethanediamine (bis-C(n)BEC), of general formula /C(n)H(2n+1)OOCCH2(CH3)2N(+)CH2CH2N(+)(CH3)2CH2COOC(n)H(2n+1)/2Cl-, were investigated (n=10, 12, 14). The interaction with model membrane was studied by differential scanning calorimetry experiments, and the apparent adiabatic molar compressibility of their solution as a function of concentration was obtained by sound velocity measurements. Their biological activities were assayed by Electrophoresis Mobility Shift, MTT proliferation, and transient transfection.

Antimicrobial activity of N-alkoxycarbonylmethyl-N-alkyl-piperidinium chlorides.

The aim of the study was to assay antibacterial and antifungal activity of newly synthesised N-alkoxycarbonylmethyl-N-alkyl-piperidinium chlorides. The compounds tested were found to inhibit the growth of some Gram-negative bacteria, Gram-positive strains and some representatives of yeast-type Candida. From microbiological experiments two of the compounds tested, N-dodecyloxycarbonylmethyl-N-methyl-piperidinium chloride (3) and N-dodecyl-N-ethoxycarbonylmethyl-piperidinium chloride (6), emerged as more active than the other compounds.

A study on the interaction between 1-decyloxymethyl-3-carbamoylpyridinium salts and model membranes--the effect of counterions.

The interaction between 1-decyloxymethyl-3-carbamoylpyridinium salts (PS-X) and two types of vesicles (multilamellar vesicle and sonicated vesicle) was investigated. Vesicles were formed from two classes of phospholipids: 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (DPPE). The PS-X salts used had nitrate, perchlorate, tetrafluoroborate and halides as counterions.

Interaction between N-dodecyl-N,N-dimethyl-N-benzylammonium halides and phosphatidylcholine bilayers-the effect of counterions.

The interaction of N-dodecyl-N,N-dimethyl-N-benzylammonium halides (DBeAX) with two types of phospholipid vesicles (MLV and SUV) was investigated using DSC and 1H NMR. It was suggested that the benzyl group like the micellisation process (J. Colloid Interface Sci.

Influence of dodecyltrimethylammonium halides on interaction of phenyltin compounds with model membranes.

The effects were studied of dodecyltrimethylammonium chloride (DTAC), dodecyltrimethylammonium bromide (DTAB) and dodecyltrimethylammonium iodide (DTAI) on thermotropic phase behaviour of phosphatidylcholine bilayers, as well as on 1H NMR and 31P NMR spectra, in the presence of diphenyltin dichloride (DPhT) and triphenyltin chloride (TPhT). The obtained results indicate that in the presence of the surfactant studied the interaction of phenyltin compounds with model membranes was changed and the changes depended on the kind of the counterion. The surfactants studied (especially DTAC) decrease the ability of phenyltin compounds to induce structural changes in the bilayer.

Counterion effects on interaction of amphiphilic quaternary ammonium salts with model membranes.

The micellization as well as the interaction with model membranes of dodecyltrimethylammonium halides (DTAX) and N-dodecyl-N,N-dimethyl-N-benzylammonium halides (DBeAX) were studied at 298K and 313K by means of titration calorimetry. The calorimetric curves reflect both the counterion and benzyl group effects on the interaction of the surfactants studied with the lipid bilayer. Bromide as counterion enhanced the interactions more than chloride of both DTAX and DBeAX compounds with model membranes.

Micellization process--temperature influence on the counterion effect.

The micellization process of dodecyltrimethylammonium chloride (DTAC) and bromide (DTAB) was studied at 313 K. Nuclear magnetic resonance and calorimetric methods were used. The calorimetric titration curves permitted determination of the critical micelle concentration (CMC) and enthalpy of the micellization process (deltaHm) of the compounds studied.

Influence of dodecyltrimethylammonium halides on thermotropic phase behaviour of phosphatidylcholine/cholesterol bilayers.

Effects of dodecyltrimethylammonium chloride (DTAC), dodecyltrimethylammonium bromide (DTAB) and dodecyltrimethylammonium iodide (DTAI) on thermotropic phase behaviour of phosphatidylcholine bilayers containing cholesterol as well as on 1H NMR spectra were studied. Two series of experiments were performed. In the first one the surfactants were added to the water phase while in the other directly to the lipid phase (a mixed film from cholesterol, surfactant and phosphatidylcholine was formed).

Hydration of alkylammonium salt micelles--influence of bromide and chloride counterions.

The micellization process of dodecyltrimethylammonium chloride (DTAC) and bromide (DTAB) was studied. Nuclear magnetic resonance method was used. The 1H NMR and 13C NMR spectra were taken at higher and lower concentrations than the critical micelle concentrations (CMC) of the compounds studied.

Effect of counterions on the influence of dodecyltrimethylammonium halides on thermotropic phase behaviour of phosphatidylcholine bilayers.

Effects of dodecyltrimethylammonium chloride (DTAC), dodecyltrimethylammonium bromide (DTAB) and dodecyltrimethylammonium iodide (DTAI) on thermotropic phase behaviour of phosphatidylcholine bilayers as well as on 1H NMR spectra were studied. In order to enhance the effect of counterions on water structure two series of experiments were performed. In the first one the surfactants were added to the water phase and in the other one directly to lipid phase (a mixed film was formed).

Influence of counterions on the interaction of pyridinium salts with model membranes.

The interaction of pyridinium salts (PS) with red blood cells and planar lipid membranes was studied. The aim of the work was to find whether certain cationic surfactant counterion influence its possible biological activity. The counterions studied were Cl-, Br-, I-, ClO4-, BF4- and NO3-.

1H NMR Studies of Aqueous Micellar Solutions of N-Dodecyl- N,N-dimethyl-N-benzylammonium Chloride.

(1)H NMR studies of the micellization process in N-dodecyl-N,N-dimethyl-N-benzylammonium chloride (DBeAC) were carried out. The spectra were measured at concentrations below and above the critical micelle concentration (CMC). The chemical shifts and Nuclear Overhauser Effect (NOE) measurements were analyzed as a function of the concentration.

The role of counterions in the interaction of bifunctional surface active compounds with model membranes.

Interaction of two series of bifunctional surfactants (bromides and chlorides) with red blood cells and planar lipid membranes was studied. The aim of the work was to determine the role of counterions in the mechanism of interaction of bifunctional cationic surfactants with model membranes. In each case bromides influenced model membranes to a greater degree than the corresponding chlorides.

Interaction between model membranes and a new class of surfactants with antioxidant function.

The effect of two series of amphiphilic quaternary ammonium salts on some properties of phospholipid membranes was studied. The compounds of one series, N-benzyl-N,N-dimethyl-N-alkyl ammonium bromides, exert a destructive effect on membranes and are treated as reference compounds. The compounds of the other series, N-(3,5-di-t-butyl-4-hydroxy)benzyl-N,N-dimethyl-N-alkyl ammonium bromides, are derivatives of the former ones, exhibit antioxidant properties, and do only relatively slight damage to the membranes.