Influence of doxorubicin inclusion into phospholipid nanoformulation on its antitumor activity in mice: increased efficiency for resistant tumor model

Aim: The new formulation of doxorubicin on the base of phospholipid nanoparticles (particle size <30 nm) is elaborated in the Institute of Biomedical Chemistry (Russian Academy of Medical Sciences) on the base of plant phospholipids. The aim of study is to investigate an antitumor effect of this nanoformulation in mice with two cancer models with various sensitivity to chemotherapy — lymphoid malignancy P-388 and Lewis lung carcinoma (LLC). Methods: Nanophospholipid (NPh) formulation of doxorubicin was prepared by homogenization of soybean phosphatidylcholine and doxorubicin hydrochloride. The effect of this formulation was studied in experiments with single or threefold drug administration. Percents of tumor growth inhibition in mice under influence of free or NPh doxorubicin forms were compared. Results: Single administration of both free and NPh doxorubicin in mice with P-388 resulted in the same quick severe inhibition of tumor growth (60–90% depending from dose), with further gradual decrease of inhibition degree. However for more resistant tumor, LLC, the obvious advantage of NPh doxorubicin form was shown. The little effect of free doxorubicin began to reveal only after 11 days, but NPh formulation induced significant inhibition of tumor growth (40%) from the first experimental point (6 days after administration). The advantages of NPh doxorubicin was manifested particularly in low drug doses, 2 and 4 mg/kg. In other experiment design in mice with LLC, with threefold weekly drug administration, NPh doxorubicin appeared to be 2.5 times more active than free drug. The reason of the same actions of free and NPh doxorubicin form in P-388 is suggested the high drug sensitivity of this model, that gives quick high drug response for any doxorubicin form. Conclusion: Doxorubicin in phospholipids nanoformulation revealed higher antitumor efficiency as compared with free doxorubicin in mice with LLC carcinoma. The mechanism of such changes is supposed to be caused by increase of doxorubicin availability for cancer cells

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Shape memory effect and superelasticity in single-phase nickel titanium single crystals

On Ti-50.3%Ni and Ti-48%Ni-2%Fe (at.%) single crystals of [001], [111], [139], [123] orientations the influence of preliminary deformation of martensitic phase and aging (marforming) on shape memory effect (SME) and superelasticity (SE) has been investigated. It has been shown that marforming leads to occurrence of SE, which is absent in initial state

The effect of aluminium on mechanical properties and deformation mechanisms of hadfield steel single crystals

On single crystals of Hadfield steel (Fe-13Mn-1.3C, Fe-13Mn-2.7Al-1.3C, wt.%) the systematical investigations of deformation mechanisms - slip and twinning, stages of plastic flow, strain hardening coefficient depending on orientation of tensile axis have been carried out by methods of optical and electron microscopy, x-ray analysis. Is has been shown that the combination of low stacking fault energy ($\gamma_{\rm{SF}}=0.03$J/m$^2$) with high concentration of carbon atoms in aluminium-free steel results in development of the mechanical twinning at room temperature in all crystal orientations. The new type of twinning with formation of extrinsic stacking fault has been found out in [001] single crystals. Experimentally it has been established that alloying with aluminium leads to increase of stacking fault energy of Hadfield steel and suppresses twinning in all orientations of crystals at preservation of high values of strain-hardening coefficients $\theta$