Critical roles of cationic surfactants in the preparation of colloidal mesostructured silica nanoparticles: control of mesostructure, particle size, and dispersion.

Mesoporous silica nanoparticles are promising materials for various applications, such as drug delivery and catalysis, but the functional roles of surfactants in the formation and preparation of mesostructured silica nanoparticles (MSN-as) remain to be seen. It was confirmed that the molar ratio of cationic surfactants to Si of alkoxysilanes (Surf/Si) can affect the degree of mesostructure formation (i.e., whether the mesochannels formed inside the nanoparticles actually pass through the outer surface of the particles), the particle diameter, and the dispersibility of MSN-as. Wormhole-like mesostructures formed with low Surf/Si ratios; however, the mesopores did not pass through the outer surface of the particles completely. At high Surf/Si ratios, the mesostructures extended. The particle diameter was 100 nm or larger at low Surf/Si ratios, and the primary particle diameter decreased as the Surf/Si ratio increased. This was because the surfactants enhanced the dispersity of the alkoxysilanes in water and the hydrolysis rate of the alkoxysilanes became faster, leading to an increased nucleation as compared to the particle growth. Moreover, primary particles aggregated at low Surf/Si ratios because of the hydrophobic interactions among the surfactants that were not involved in the mesostructure formation but were adsorbed onto the nanoparticles. At high Surf/Si ratios, the surfactant micelles were adsorbed on the surface of primary particles (admicelles), resulting in the dispersion of the particles due to electrostatic repulsion. In particular, molar ratios of 0.13 or higher were quite effective for the preparation of highly dispersed MSN-as. Surfactants played important roles in the mesostructure formation, decreasing the particle diameters, and the dispersibility of the particles. All of these factors were considerably affected by the Surf/Si ratio. The results suggested novel opportunities to control various colloidal mesostructured nanoparticles from the aspects of composition, structure, and morphology and will also be useful in the development of novel methods to prepare nanomaterials in various fields.

Aqueous colloidal mesoporous nanoparticles with ethenylene-bridged silsesquioxane frameworks.

Aqueous colloidal mesoporous nanoparticles with ethenylene-bridged silsesquioxane frameworks with a uniform diameter of ∼20 nm were prepared from bis(triethoxysilyl)ethenylene in a basic aqueous solution containing cationic surfactants. The nanoparticles, which had higher hydrolysis resistance under aqueous conditions, showed lower hemolytic activity toward bovine red blood cells than colloidal mesoporous silica nanoparticles.

Dialysis process for the removal of surfactants to form colloidal mesoporous silica nanoparticles.

Colloidal mesoporous silica nanoparticles less than 20 nm in diameter are prepared by dialysis; this simple surfactant removal route can avoid aggregation by sedimentation-redispersion and remove cationic surfactants while retaining the original colloidal state, which is applicable to the preparation of primary nanoparticles carrying a functional organic substance.

Fabrication of hierarchically porous spherical particles by assembling mesoporous silica nanoparticles via spray drying.

A new type of hierarchically porous materials is fabricated by assembling mesoporous nanoparticles via spray drying. Well-dispersed mesostructured silica nanoparticles (MSN), whose particle size distribution was narrow in the range of 20 nm and 50 nm, were prepared by a thermal deposition method. By spray drying a MSN suspension, MSN were assembled into spherical secondary particles. After calcination, the spherical particles have two types of mesopores, mesopores of 3 nm in size inside of calcined MSN and larger inter-nanoparticle mesopores of about 15-20 nm. This hierarchical pore system should provide nanospaces for efficient mass transport of guest species with different sizes.

In vitro activity of lauric acid or myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA).

The objective of this study was to investigate the in vitro activities of lauric acid and myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA). The combination effect of lipids and antimicrobial agents was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index. The effects of lauric acid + gentamicin (GM) and lauric acid + imipenem (IPM) combinations were synergistic against the clinical isolates in 12 combinations. An antagonistic FIC index was observed only with the myristylamine + GM combination. We investigated in detail the antimicrobial activity for two combinations that showed a synergistic effect. The cytotoxicity of lauric acid was not enhanced by the addition of GM and IPM. In time-kill studies, lauric acid + GM and lauric acid + IPM combinations at one-eighth of the minimum inhibitory concentration produced a bacteriostatic effect.

Antimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus.

The objective of this study was to investigate the antimicrobial activities of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of saturated fatty acids and fatty amines was determined by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the saturated fatty acids, showed antimicrobial activity at 400 microg/ml against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concentration (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 microg/ml; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, respectively. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 saturated fatty acids and 3 fatty amines was examined in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of saturated fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, especially in the case of insoluble substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.

Experimental studies on the effects of the combined use of N-(4-hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) for estrogen receptor (ER)-negative breast cancer.

We investigated the effects of combination therapy with N-(4-hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) on estrogen receptor (ER) negative breast cancer, for which no effective supplementary therapy has been established, using the human breast cancer cell line MDA-MB-231. TAM or 4-HPR alone had little antitumor effect, but the combined use of TAM and 4-HPR had a strong cell growth inhibitory effect. Cell cycle analysis by flow cytometry showed an increased frequency of the G2/M phases in the 4-HPR-TAM combination group. Measurement of 3H-TAM incorporation into the cell showed that, compared with the TAM group, the 4-HPR-TAM combination group incorporated about 1.45 times more TAM into the cell. Thin-layer chromatographic analysis of changes in the cell membrane ganglioside GM3 showed a marked increase in GM3 in the 4-HPR-TAM combination group. We speculate that the administration of TAM in the presence of 4-HPR changes the membrane glycolipid GM3, increasing intracellular TAM concentrations, thus exerting antitumor activity. Presumably, during this process, antitumor effects do not induce cell death but arrest the cell cycle in the G2 phase. Thus, the combined use of TAM and 4-HPR inhibited the growth of the ER-negative breast cancer cell line MDA-MB-231. These results suggest that combination therapy with TAM and 4-HPR can be a potent supplementary therapy also for ER-negative patients in clinical practice.