Chisato Takahashi

Physicochemical Characterization of Cyclodextrin–Drug Interactions in the Solid State and the Effect of Water on These Interactions

The characterization of cyclodextrin (CD)-drug interactions has encountered difficulties in the solid state, especially of amorphous state. However, recent advances in experimental techniques, such as X-ray diffraction, spectroscopy, thermal analysis, and solid-state nuclear magnetic resonance, as well as computational chemistry have provided new insights in this area. Furthermore, inclusion complexes have been found to originate from noncovalent interactions, such as van der Waals and hydrogen bonding. The formation of CD hydrates and inclusion complexes in the solid state is considered to only rely on intermolecular interactions, without any covalent bond rupture and formation in host and guest molecules. The presence of water molecules as special guests impacts on the solid-state arrangement of CD molecules, which makes this influence important to consider. Accordingly, this review presents an overview of recent work about the physicochemical characterization of CD-drug interactions in the solid state with a focus on the effect of water molecules on these interactions.

FE-SEM observation of swelled seaweed using hydrophilic ionic liquid; 1-butyl-3-methylimidazolium tetrafluoroborate

The method to observe the exact morphology of swelled seaweed as an example of biological material by field emission scanning electron microscopy (FE‐SEM) with the aid of hydrophilic ionic liquid (IL); 1‐butyl‐3‐methylimidazolium tetrafluoroborate is reported. Seaweed was first swelled in 3.5% NaCl solution and then treated with the IL and water mixture in 1:7 weight ratios and centrifuged to remove the excess IL solution. Thus treated seaweed maintained its morphology even at high magnification and did not show drying in the FE‐SEM chamber. This observation technique might be useful for various kinds of biological materials to be observed under FE‐SEM. Microsc. Res. Tech., 2013.

Field emission characteristics of pristine and N-doped graphene measured by in-situ transmission electron microscopy

We report the field emission characteristics of a few-layer pristine and N-doped graphene by the in-situ transmission electron microscopy. The measurements were performed with a Pt-Ir nanoprobe and at a vacuum gap of 400 nm. The turn on voltage, required to draw an emission current of 1 nA from pristine and N-doped graphene, was found to be 230 and 110 V, respectively. The lower turn on voltage for the N-doped graphene can be explained from the improved electrical conductivity and up-shift of the Fermi level with nitrogen doping. Structural deformation/contraction/buckling of the N-doped graphene sheet was observed with the field emission current exceeding ∼6.9 μA, which can be attributed to the Joule heating.

Observation of antibacterial effect of biodegradable polymeric nanoparticles on Staphylococcus epidermidis biofilm using FE-SEM with an ionic liquid

We successfully visualized the antibacterial behavior of biodegradable polymeric nanoparticles (NPs) on a biofilm formed by Staphylococcus epidermidis using field emission scanning electron microscopy (FE-SEM). A hydrophilic ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]), was applied for observation using FE-SEM. The differences in adherence and penetration behavior of three types of NPs were revealed using this method and confocal laser scanning microscopy. Biodegradable poly(dl-lactide-co-glycolide) (PLGA) NPs were prepared by the emulsion solvent diffusion method. In this study, we treated the biofilm with three PLGA NPs: unmodified PLGA, PLGA modified with chitosan (CS) and clarithromycin (CAM)-loaded + CS-modified PLGA. The viability of S. epidermidis cells treated with PLGA NPs was estimated using the LIVE/DEAD BacLight kit to understand the antibacterial ability of each NP sample in a quantitative way. The results confirmed that CAM-loaded + CS-modified PLGA had high antibacterial ability on the biofilm. This novel observation technique would be useful in the development of drug formations and medical agents.

Field emission properties of chemical vapor deposited individual graphene

Here, we report field emission (FE) properties of a chemical vapor deposited individual graphene investigated by in-situ transmission electron microscopy. Free-standing bilayer graphene is mounted on a cathode microprobe and FE processes are investigated varying the vacuum gap of cathode and anode. The threshold field for 10 nA current were found to be 515, 610, and 870 V/μm for vacuum gap of 400, 300, and 200 nm, respectively. It is observed that the structural stability of a high quality bilayer graphene is considerably stable during emission process. By contacting the nanoprobe with graphene and applying a bias voltage, structural deformation and buckling are observed with significant rise in temperature owing to Joule heating effect. The finding can be significant for practical application of graphene related materials in emitter based devices as well as understanding the contact resistance influence and heating effect.

Visualizing copper assisted graphene growth in nanoscale.

Control synthesis of high quality large-area graphene on transition metals (TMs) by chemical vapor deposition (CVD) is the most fascinating approach for practical device applications. Interaction of carbon atoms and TMs is quite critical to obtain graphene with precise layer number, crystal size and structure. Here, we reveal a solid phase reaction process to achieve Cu assisted graphene growth in nanoscale by in-situ transmission electron microscope (TEM). Significant structural transformation of amorphous carbon nanofiber (CNF) coated with Cu is observed with an applied potential in a two probe system. The coated Cu particle recrystallize and agglomerate toward the cathode with applied potential due to joule heating and large thermal gradient. Consequently, the amorphous carbon start crystallizing and forming sp2 hybridized carbon to form graphene sheet from the tip of Cu surface. We observed structural deformation and breaking of the graphene nanoribbon with a higher applied potential, attributing to saturated current flow and induced Joule heating. The observed graphene formation in nanoscale by the in-situ TEM process can be significant to understand carbon atoms and Cu interaction.

Electron microscopy of Staphylococcus epidermidis fibril and biofilm formation using image-enhancing ionic liquid

We established an optimized biofilm observation method using a hydrophilic ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]). In the present study, a biofilm was formed by Staphylococcus epidermidis. Using field emission (FE) scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the colonization of assemblages formed by microbial cells was observed as a function of the cultivation time. FE-TEM analysis revealed that the fibril comprises three types of protein. In addition, the ultrastructure of each protein monomer was visualized. It was expected that the curly-structured protein plays an important role in extension during fibril formation. Compared to the conventional sample preparation method for electron microscopy, a fine structure was easily obtained by the present method using IL. This observation technique can provide valuable information to characterize the ultrastructure of the fibril and biofilm that has not been revealed till date. Furthermore, these findings of the molecular architecture of the fibril and the colonization behavior of microbial cells during biofilm formation are useful for the development of antibacterial drugs and microbial utilization.

Improvement in the water solubility of drugs with a solid dispersion system by spray drying and hot-melt extrusion with using the amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and d-mannitol

ABSTRACT The aim of this study was to prepare and characterize solid dispersion particles with a novel amphiphilic polyvinyl caprolactam‐polyvinyl acetate‐polyethylene glycol graft copolymer, as a water‐soluble carrier. Solid dispersion particles were prepared by hot‐melt extrusion and spray drying. Indomethacin (IMC) was used as a model comprising drugs with low solubility in water and d‐mannitol (MAN) was used as an excipient. The physicochemical properties of prepared particles were characterized by scanning electron microscopy, thermal analysis, powder X‐ray diffraction (PXRD) analysis, FTIR spectra analysis, and drug release studies. Stability studies were also conducted under stress conditions at 40 °C, 75% relative humidity. We found that dissolution behavior of the original drug crystal could be improved by solid dispersion with the polyvinyl caprolactam‐polyvinyl acetate‐polyethylene glycol graft copolymer. The PXRD pattern and thermal analysis indicated that the solid dispersion prepared with the polyvinyl caprolactam‐polyvinyl acetate‐polyethylene glycol graft copolymer and IMC was in an amorphous state. FTIR spectra analysis indicated that the interaction manner between the polyvinyl caprolactam‐polyvinyl acetate‐polyethylene glycol graft copolymer and IMC may differ with the preparation method and formulation of solid dispersions. Stability studies proved that the amorphous state of IMC in solid dispersion particles was preserved under stress conditions for more than two weeks. Graphical abstract Figure. No Caption available.

Visualization of silver-decorated poly (DL-lactide-co-glycolide) nanoparticles and their efficacy against Staphylococcus epidermidis

Understanding of self-protection activity of the bacteria and interaction with drug substances has significant importance for designing of effective drug delivery system for treatment of biofilm infections. Recently silver nanoparticle has attracted attention as antibacterial substance for drug delivery system because of its high antibacterial activity. Here, efflux of silver nanoparticles obtained from within the prepared silver-decorated poly (DL-lactide-co-glycolide) (Ag PLGA) nanoparticles derived from Staphylococcus epidermidis bacterial cell was successfully visualized using scanning transmission electron microscopy (STEM). We also revealed the interaction between prepared Ag PLGA nanoparticles and the bacterial cells at the nanoscale level using field emission scanning electron microscopy and STEM, after a pretreatment process by an ionic liquid. This finding is significant to understand a fundamental function of S. epidermidis bacterial cells, which is not explored previously. The results suggest that Ag PLGA nanoparticles could demonstrate high efficacy against biofilm infections.

Interaction of fentanyl with various cyclodextrins in aqueous solutions

Water‐soluble fentanyl citrate salt has been used in sublingual or buccal formulations for the breakthrough pain treatment. However, fentanyl absorption through the lipid mucosal membrane may be improved by enhancing the non‐ionic lipophilic fentanyl base solubility. Therefore, the interaction between cyclodextrins (CDs) and fentanyl base has been evaluated to obtain basic information for its application.