Synthesis of methotrexate-betulonic acid hybrids and evaluation of their effect on artificial and Caco-2 cell membranes.

An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids with a (tert-butoxycarbonylamino)-3,6-dioxa-8-octanamine (Boc-DOOA) linkage has been developed. Reaction of N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-betulonamide with methotrexate resulted in a mixture of isomeric conjugates which were separated by column chromatography. Their structures and composition have been fully established by H NMR, C spectra, FAB mass spectrometry and elemental analysis.

Thermoresponsive cholesteric liquid-crystal systems doped with terpenoids as drug delivery systems for skin applications.

Stimuli-responsive and tunable soft-matter systems are an advanced class of materials applicable for drug delivery. Liquid crystals (LCs) are promising candidates as multifunctional materials that can respond to temperature, light or magnetic field. Particularly, ordering and physical properties of thermoresponsive LCs depend predominantly on temperature as external trigger.

Investigation of thioctic acid, magnesium stearate and pyridoxine hydrochloride compatibility.

To identify possible interactions of components in dosage forms, studies are usually carried out at the stage of pharmaceutical development. Such studies can predict compatibility of active pharmaceutical ingredients and excipients in order to optimize drug formulation and certain parameters of technological process. Compatibility of some components of a newly developed neuroprotective medicinal product Neuronucleos, namely, thioctic acid, pyridoxine hydrochloride, magnesium stearate and magnesium lactate, was studied by means of differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR).

Thermodynamics and kinetics of joint action of antiviral agent tilorone and DMSO on model lipid membranes.

Individual and joint action of two water-soluble drugs, DMSO and tilorone, on model l-α-dipalmitoylphosphatidylcholine (DPPC) membranes were studied in equilibrium and kinetic regimes by differential scanning calorimetry (DSC). For equilibrium experiments, the drugs were introduced during preparation of the model membrane. In kinetic studies, one of the drugs was added to the DPPC membrane already containing the other drug, and the effects of drug-membrane interactions were monitored in real-time regime.

Meaning of activation energy in phospholipid multibilayers phase transitions.

The question of the activation energy of phase transitions in lyotropic liquid crystal phases of model phospholipid membranes was considered. In our experiments, we obtained DSC thermograms of hydrated DPPC and DMPC at different scanning rates, and activation energy values were determined by a modification of Kissinger non-isothermal kinetics method. Using this approach the equivalent order of reaction corresponding to the phase transition can be determined alongside the activation energy.

[Effects of silver nitrate on the phase state of model multibilayer membranes].

In order to study the effects caused by silver nitrate (AgNO3) on model lipid membranes, we studied multibilayer membranes based on L-α-dipalmitoylphosphatidylcholine (DPPC) and AgNO3 aqueous soluitions in a wide concentration range (up to 30 wt%) by means of differential scanning calorimetry. It has been shown that the presence of AgNO3 leads both to an increase in the main phase transition temperature (T(m)) and appearance of an additional phase transition peak (T(m)), suggesting increasing of both density and heterogeneity of the lipid membrane. The effect of nitrate ions (NO ) was shown to be of the opposite nature (bilayer fluidizing), so the integral densifying effect of AgNO3 can be referred solely to the action of silver ions (Ag(+)).

Suppressed ionic effect and low-frequency texture transitions in a cholesteric liquid crystal doped with graphene nanoplatelets.

We focus on investigating the dielectric behaviors and the low-frequency texture transitions in a cholesteric liquid crystal (CLC) doped with graphene nanoplatelets (GNPs) by means of dielectric spectroscopy and measurements of electro-optical responses. The experimental results indicate that incorporating GNPs at a content of 0.5 wt% into the CLC leads to significant suppression of ionic behaviors, as manifested by the reduction in ionic density, diffusivity, and relaxation frequency.

Probing of the combined effect of bisquaternary ammonium antimicrobial agents and acetylsalicylic acid on model phospholipid membranes: differential scanning calorimetry and mass spectrometry studies.

A model molecular biosystem of hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers that mimics cell biomembranes is used to probe combined membranotropic effects of drugs by instrumental techniques of molecular biophysics. Differential scanning calorimetry reveals that doping of the DPPC model membrane with individual bisquaternary ammonium compounds (BQAC) decamethoxinum, ethonium, thionium and acetylsalicylic acid (ASA) leads to lowering of the membrane melting temperature (Tm) pointing to membrane fluidization. Combined application of the basic BQAC and acidic ASA causes an opposite effect on Tm (increase), corresponding to the membrane densification.

Optical transmission of nematic liquid crystal 5CB doped by single-walled and multi-walled carbon nanotubes.

Comparative studies of optical transmission of single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), dispersed in nematic liquid crystal matrix 5CB, were carried out. The data evidence violations of Beer-Lambert-Bouguer (BLB) law both in cell thickness and concentration dependencies. The most striking is the fact that optical transmission dependencies for SWCNTs and MWCNTs were quite different in the nematic phase, but they were practically indistinguishable in the isotropic phase.

Rotation of single crystals of chiral dopants at the top of a nematic droplet: analogy with Lehmann effect.

Detailed studies are reported of the Lehmann-type effect of rotation of small single crystals of chiral substances during their dissolution at the top of a nematic droplet, which was first noted in our previous works. The rotation effect is shown to be essentially dependent on the dopant chirality. The angular velocity of the rotation of the chiral dopant crystals is experimentally shown to be dependent on the crystal dimensions, helical-twisting power of the dopant (determined in independent measurements) and viscosity of the nematic solvent, whereas no rotation was observed for non-chiral dopants or in isotropic solvents under the same conditions.

Effects of membranotropic agents on mono- and multilayer structures of dipalmitoylphosphatidylcholine.

We have studied the action of some membranotropic agents (MTAs) on the parameters of mono- and multilayers of dipalmitoylphosphatidylcholine (DPPC). The MTAs used included an antimicrobial drug, decamethoxinum, the model amphiphilic agent stearoyl-L-alpha-alanine, and cholesterol as a reference substance. Using differential scanning calorimetry and the Langmuir monolayer technique, we measured the temperature and enthalpy of the main phase transition of DPPC, the mean molecular area, the collapse pressure and the free energy of the mixed monolayers of DPPC and MTA.

Mechanistic investigation of the interaction between bisquaternary antimicrobial agents and phospholipids by liquid secondary ion mass spectrometry and differential scanning calorimetry.

Mechanisms of interaction between the antimicrobial drugs decamethoxinum and aethonium, which are based on bisquaternary ammonium compounds, and a phospholipid component of biological membranes, dipalmitoylphosphatidylcholine, were studied by means of liquid secondary ion mass spectrometry (LSIMS) and differential scanning calorimetry (DSC). Supramolecular complexes of the drugs with this phospholipid were recorded under secondary ion mass spectrometric conditions. The dependence of the structures of these complexes on structural parameters of the dications of the bisquaternary ammonium compounds was demonstrated.