In vitro gene delivery mediated by lactosylated dendrimer (generation 3, G3)/��-cyclodextrin conjugates into hepatocytes

The purpose of this study is to evaluate in vitro gene delivery efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 3, G3) conjugates with ??-cyclodextrin (??-CDE (G3)) bearing lactose (Lac-??-CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel hepatocyte-selective carrier. Lac-??-CDE (G3, DSL 1.2) was found to have much higher gene transfer activity than ??-CDE (G3), Lac-??-CDE (G2, DSL 2.6) and Lac-??-CDEs (G3, DSL 2.6, 4.1 and 6.1) in HepG2 cells, which are dependent on the expression of cell-surface asialoglycoprotein receptor (ASGP-R). Lac-??-CDE (G3, DSL 1.2) provided negligible cytotoxicity up to a charge ratio of 100 (carrier/pDNA) in HepG2 cells. These results suggest the potential use of Lac-??-CDE (G3, DSL 1.2) as a non-viral vector for gene delivery toward hepatocytes.     

Electrical properties of Na-doped (SN)x single crystal

Electrical resistivity of (SN)_x crystal along the b-axis increases in Na ion solution by several times in a few tens of minutes. Temperature dependence of resistivity and transverse magnetoresistance at 4.2 K in Na-doped (SN)_x do not change remarkably from the pristine (SN)_x. These experimental results are discussed in terms of electron transfer from the dopant (Na) to (SN)_x into consideration, comparing with the case of halogen doping.     

Negative magnetoresistance in (SN)x single crystal

The magnetoresistance in (SN)x single crystals is composed of the normal positive and negative components. The former increases in proportion to the square of the magnetic field B². The latter is remarkable at temperatures below 4.2 K and saturates at relatively low magnetic field (? 30 kG). The coefficient $\text{S(=}\text{lim}\text{B→0}\text{{??}\text{(}\text{δρ}\text{ρ}{}_0\text{)}\text{?B}{}^2\text{})}$ of this negative magnetoresitance shows features similar to those of semiconductors with Toyozawa's theory. These results of negative magnetoresistance are explained in terms of carrier scattering by localized magnetic moments.     

Inclusion complex of 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoline-6-one (KCA-098) with heptakis(2,6-di-O-methyl)-beta-cyclodextrin: interaction and dissolution properties

Interactions of KCA-098 with heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) in solution and in the solid state were studied by the solubility method, UV and fluorescence spectroscopy, powder X-ray diffractometry, and thermal analysis. The KCA-098/DM-beta-CyD system showed an A(L) type solubility diagram with stability constants of 5870 and 2220 M(-1) in aqueous and 10% methanol solutions, respectively. Following the addition of DM-beta-CyD, the maximum UV wavelength of KCA-098 was shifted to a longer wavelength and the fluorescence intensity was decreased. A similar spectral change was observed when KCA-098 was dissolved in less polar solvents, especially in proton-acceptor solvents, such as acetone and dimethylsulfoxide, suggesting that KCA-098 interacts with DM-beta-CyD through not only a hydrophobic interaction but also hydrogen bonding. The solid complex of KCA-098 with DM-beta-CyD in a molar ratio of 1:1 was prepared by the kneading method and the solvent evaporation method, using organic solvents. Powder X-ray diffractometric and differential scanning calorimetric studies indicated that KCA-098 was dispersed as microparticles on the DM-beta-CyD complex in the solid state prepared by the solvent evaporation method although it dispersed as crystals in the sample prepared by the kneading method. The dissolution of KCA-098 from the solid complex prepared by the former method was markedly faster than that prepared by the latter method, although it slowed down with the passage of time. The reduced dissolution of KCA-098 was explained by crystallization to the hydrate form in the medium. These data indicate that poorly water-soluble KCA-098 interacts with DM-beta-CyD in water and in the solid state and that a fast-dissolving form of KCA-098 can be obtained by evaporating with DM-beta-CyD using organic solvents.     

Cell-Specific Gene Transfer by α-Cyclodextrin Conjugates with Mannosylated Polyamidoamine Dendrimers

To improve the activity and the cell specificity of gene transferof polyamidoamine starburst dendrimer, we prepared -CyD conjugates with mannosylateddendrimers (generation 2 (G2), man--CDE conjugates) having various degrees of substitution(DS) of mannose residue. The man--CDE conjugates (DS 1, 3 and 5) formed complexeswith plasmid DNA (pDNA), but man--CDE conjugate (DS 8) did not. The gene transferactivity of man--CDE conjugates (DS 1, 3 and 5) and -CDE conjugate was augmented with an increasein the charge ratio of vector/pDNA, without showing cytotoxicity. Man--CDE conjugates(DS 3 and 5) showed higher gene transfer activity than -CDE conjugate in A549 cells, whichrecognize mannose, but man--CDE conjugates (DS 1 and 8) showed almost comparable gene transfer activityto -CDE conjugate (G2). On the other hand, no appreciable enhancing effect of man--CDEconjugates (DS 3 and 5) on the transfer activity was observed in NIH3T3 cells, which do not recognizemannose. These findings suggest that man--CDE conjugates (DS 3 and 5) can be new preferablecell-specific non-viral vectors of pDNA to cells which recognize the mannose moiety.     

Anomalous dissolution behavior of the diazepam — γ-cyclodextrin complex in polymer solutions

The dissolution process of the diazepam — -cyclodextrin complex in aqueous polymer solutions has been studied. Hydroxypropyl cellulose and polyvinylpyrrolidone stabilize the supersaturated state of the complex, maintaining the higher drug level for a longer period. Polyethyleneglycol and dextran accelerated the dissociation of the complex, and caused a rapid decrease in drug concentration. These anomalous dissolution behaviors are discussed on the basis of viscosity changes of the polymer solutions along with the competitive interaction of polymers for the inclusion complex.     

Reduction of photohemolytic activity of benoxaprofen byβ-cyclodextrin complexations

Inclusion complexations of benoxaprofen (BXP) with-cyclodextrin (-CyD) and heptakis (2,6-di-O-methyl)--CyD (DM--CyD) were studied by the solubility method and CD and¹H-NMR spectroscopy. Both -CyDs decelerated the photodecarboxylation of BXP, and suppressed the BXP-photosensitized hemolysis, where the inhibitory effect of DM--CyD was larger than that of -CyD. This order was well correlated with the magnitude of the stability constants of BXP--CyD complexes. The peroxidation of lipid components in erythrocyte ghosts induced by BXP was also suppressed particularly by DM--CyD. The protective effect of -CyDs on the BXP-induced photohemolysis seems to be due to the suppression in the photochemical reactions of BXP yielding toxic transient species, together with the inhibition in attacks of the transient species to the membrane, through inclusion complexation.