Biomedical subjects

Junji Watanabe

Publications and source records attributed to Junji Watanabe.

At least 55 records · Page 3Linked to original sources

PubMed2003

The Christiansen effect of brightly colored colloidal dispersion with an amphiphilic polymer.

A novel coloration phenomenon in a colloidal dispersion with an amphiphilic polymer was found. The dispersion consists of tetrahydrofuran (THF), an aqueous solution of sodium thiosulfate (Na(2)S(2)O(3).5H(2)O), and hydroxypropylcellulose (HPC). The dispersion was emulsified by HPC as an amphiphilic polymer, so that the aqueous phase was confined in droplets in the THF matrix. It typically appeared bluish violet at room temperature and turned into blue with increasing temperature. In this system, the refractive indices of the inside and outside of the droplet coincided at a certain wavelength at which the light passes through without scattering, which is called the Christiansen effect. The color observed was successfully simulated by Mie's scattering theory in combination with the Christiansen effect.

Journal Article↗

PubMed2003

Endotoxins stimulate neutrophil adhesion followed by synthesis and release of platelet-activating factor in microparticles.

Lipopolysaccharides and triacyl-cysteine-modified proteins of Gram-negative and positive organisms are potent endotoxins. Animal models show that the receptor for platelet-activating factor (PAF) is responsible for many of the deleterious effects of endotoxin, where regulated, localized PAF production localizes the inflammatory response. In contrast, biologically active analogs of PAF (PAF-like lipids) are generated by oxidative attack on phospholipids by chemical reactions that are unregulated and unlocalized. The identity and distribution of the PAF receptor ligand in endotoxemia is unknown. We found human polymorphonuclear leukocytes (PMNs) were a significant source of PAF receptor agonists after stimulation by either class of endotoxin. Production of PAF receptor agonists required that the PMN adhere to a surface, and adhesion (and therefore accumulation of PAF-like bioactivity) in response to endotoxic stimulation was delayed for several minutes. PAF-like oxidized phospholipids were found by mass spectroscopy, but biosynthetic PAF accounted for most of the phospholipid agonists arising from endotoxic stimulation. A significant portion of the PAF made by PMNs was secreted, in contrast to its near complete retention by other inflammatory cells. Endotoxic stimulation induced a respiratory burst with the production of superoxide and the formation and shedding of microparticles. Free and microparticle-bound PAF appeared in the media, and blocking microvesiculation with calpeptin blocked PAF release. The released material activated platelets, and platelets co-aggregated with endotoxin-stimulated PMNs. Adherent PMNs therefore behave differently than suspended cells and are a significant source of free PAF after endotoxin exposure. Leukocytes can couple endotoxic challenge to the widespread circulatory and inflammatory effects of endotoxin.

Blood Platelets↗

PubMed2003

Surface treatment of silicon carbide using TiO2(IV) photocatalyst.

Silicon carbide (SiC) and diamond were decomposed to CO(2)(g) by the photocatalysis with TiO(2) at room temperature, although the decomposition rate of diamond was very slow. According to the XPS spectra of Si2p on the SiC surface, SiO(2) was simultaneously formed on the surface by the TiO(2) photocatalysis. The thickness of the SiO(2) formed on the SiC surface during the photocatalytic oxidation for 1 h was estimated to be about 40 A from the depth profile of the XPS spectra using Ar etching. The SiC surface was oxidized by the TiO(2) photocatalysis even under the condition without a direct contact with the TiO(2). This indicates that the photocatalytic oxidation of the SiC occurs due to active oxygen species photogenerated on the TiO(2) surface, but not by hole produced in the valence band of the TiO(2). Moreover, a remote surface treatment system using the quartz beads coated with TiO(2) was developed for the SiC surface oxidation. Consequently, the TiO(2) photocatalysis will be very useful for the surface treatment of SiC such as photopatterning without defects and damage to the substrate because the photocatalytic reaction is carried out under mild conditions.

Journal Article↗

PubMed2003

Enhanced solubility of paclitaxel using water-soluble and biocompatible 2-methacryloyloxyethyl phosphorylcholine polymers.

The purpose of this study was to enhance the water-solubility of paclitaxel (PTX) using an amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer as the solubilizer. PTX is an antineoplastic drug effective for various cancers, especially for ovarian and breast cancers. However, its solubility in aqueous medium is quite low, less than 0.1 microg/mL in water. We prepared the amphiphilic MPC polymers containing hydrophobic units to form aggregates and provide hydrophobic domains in water. The most effective polymer to dissolve the PTX was poly[MPC-co-n-butyl methacrylate(BMA) (PMB30W)] with 70 mol % of the BMA unit. The inside polarity of PMB30W aggregate was the same as that of ethanol, which is a good solvent for dissolving PTX. The diameter of PMB30W aggregate containing 1 mg/mL of PTX was 50 nm in aqueous medium. The concentration of PTX in the PMB30W aqueous solution reached 5.0 mg/mL. The solution was transparent and PTX did not precipitate even when the solution was stored at room temperature for 1 month. Animal experiments indicated that the PMB30W has no adverse effect even when the polymer solution is injected into the bloodstream. From the PMB30W/PTX solution, we prepared by the solvent evaporation method a PMB30W film containing PTX with good transparency. The PMB30W film containing PTX easily dissolved in water to give a clear solution. We conclude that the water-soluble amphiphilic MPC polymers are good solubilizers for PTX as injectable and biocompatible drug formulations.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Antifouling blood purification membrane composed of cellulose acetate and phospholipid polymer.

The ideal surface of an artificial blood purification membrane needs hemocompatibility and durability of high performance; it should not adsorb any proteins or cells but should still have high permeability in the desired range of solute size. To improve the anti-fouling property of cellulose acetate (CA) membranes, a CA membrane blended with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (PMB30) was designed as a blood purification membrane. The polymer solutions for preparing the membrane were prepared using a solvent mixture composed of N, N-dimethylformamide, acetone, 2-propanol or water. The CA and CA/PMB30 blend membranes with an asymmetric and porous structure were prepared by a phase inversion process. The characteristics of the CA/PMB30 blend membrane, such as structural properties, mechanical properties, and solute permeability were examined with attention to changes in the preparation conditions of the membrane. The CA/PMB30 blend membrane had good water and solute permeability and a sharp molecular weight cut-off property. Moreover, the amount of proteins adsorbed on the CA/PMB30 blend membrane surface was less than that of the original CA membrane and a conventional polysulfone membrane. Adhesion and activation of platelets on the CA/PMB30 blend membrane were reduced compared with that on a CA membrane. In addition, the CA/PMB30 blend membrane showed good permselectivity and an antifouling property during a long time ultrafiltration experiment with protein solutions.

2-Propanol↗

PubMed2003

Degradation of phospholipid polymer hydrogel by hydrogen peroxide aiming at insulin release device.

The purpose of this study is to ascertain the applicable possibility of H(2)O(2) degradable hydrogel for fabrication of insulin release system synchronized with the change in the glucose concentration in the medium. The hydrogel was prepared by using 2-methacryloyloxyethyl phosphorylcholine (MPC) and crosslinker. The favorable characteristic of the hydrogel was H(2)O(2) concentration responsive degradation. The H(2)O(2) was utilized and produced by enzymatic reaction between glucose oxidase and glucose. Poly(MPC) (PMPC) was easily degraded in H(2)O(2) aqueous solution, and the PMPC hydrogel was also degraded in H(2)O(2) aqueous solution. The degradation mechanism was considered to be main chain scission of PMPC. The degradation profile was evaluated by using weight swelling ratio and volume swelling ratio. The weight swelling ratio of PMPC hydrogel firstly increased due to the reduction of crosslink density, then the ratio decreased to zero (complete degradation). The degradation profile was proportional to the H(2)O(2) concentration. Furthermore, volume swelling ratio also increased, and complex elastic modulus decreased with degradation in H(2)O(2) aqueous solution. These results indicated that the hydrogel was degraded by hydroxy and/or hydroperoxy radicals which was produced by H(2)O(2), the crosslink density and mechanical property decreased. The release profile from the hydrogel was estimated by using lipid microsphere (LM) as an insulin model. The LM was released with the degradation of PMPC hydrogel. Taking these results into account, the PMPC hydrogel was available for H(2)O(2) degradable hydrogel for synchronization with glucose concentration by using enzymatic reaction.

Absorbable Implants↗

PubMed2003

Phosphorylcholine and poly(D,L-lactic acid) containing copolymers as substrates for cell adhesion.

Fibroblast cell culture was performed to evaluate cell adhesion and cell morphology on novel hydrolyzable copolymers composed of poly(D,L-lactic acid) (PDLA) macromonomer, 2-methacryloyloxyethyl phosphorylcholine (MPC), and n-butyl methacrylate. The copolymers were used as cell culture materials for regulating the interaction between the cells and the polymer surface. The results of X-ray photoelectron spectroscopy (XPS) confirmed that the PDLA chains and MPC units were present in the copolymer coating on PET films. Cell adhesion and morphology of adherent cells on coatings of the copolymers were studied. The number of cells on the surface increased with the PDLA content of the copolymer. As for the cell morphology, a round shape was observed on copolymers containing MPC units. These findings suggest that the cells recognize the PDLA and MPC units on the surface via changes in protein adsorption and/or conformation, and that the numbers of adhering cells and the cell morphology can be regulated by the composition of the copolymer.

Animals↗

PubMed2002

Theory of polar biaxial nematic phases.

A theoretical model is proposed for describing the polar biaxial and uniaxial nematic phases observed in thermotropic liquid crystals formed from rodlike polyester molecules. The polarity and biaxiality are shown to result from the same molecular mechanism, i.e., they are associated with the same critical order parameter which consists of two vectors determining the average molecular orientations in the biaxial and uniaxial phases. The model allows us to determine the critical behavior and electric or magnetic field effects that characterize polar nematic phases and to analyze, at the phenomenological and molecular levels, remarkable properties that have been disclosed experimentally.

Journal Article↗

PubMed2002

Polar structure in a ferroelectric bent-core mesogen as studied by second-harmonic generation.

Second-harmonic generation (SHG) measurements have been conducted in the ferroelectric liquid crystalline phase of a chiral bent-core molecule, P-8-OPIMB6*. Well-aligned cells were obtained by applying an electric field parallel to the substrate surfaces. In-plane anisotropy of the SHG signal observed at normal incidence of light shows two- or four-leaf patterns depending on polarization conditions, indicating a ferroelectric uniform structure. The detailed analysis of the data by taking account of optical anisotropy in the SHG active bulk leads to the determination of nonlinear susceptibility tensor components, d(333)=14.4 pm/V and d(311)=49.2 pm/V. Using the d coefficients thus determined, the hyperpolarizability tensor components of the molecule are also determined as beta(zzz)=14.5 x 10(-30) esu and beta(zxx)=67.6 x 10(-30) esu. These values well agree with those of the achiral homolog P-12-OPIMB previously determined by hyper-Rayleigh scattering.

Journal Article↗

PubMed2002

Enhancement of twisting power in the chiral nematic phase by introducing achiral banana-shaped molecules.

Achiral banana-shaped molecules with dodecyloxy tail groups, P-12-O-PIMB, N-12-O-PIMB, and S-12-O-PIMB, have exhibited unusual smectic phases which possess chiral and helical structures. In this work, we mixed these banana-shaped molecules with the chiral molecule forming a chiral nematic liquid crystal and found an exclusive effect of the achiral dopant that the twisting power of the chiral nematic phase in the mixtures is significantly increased with the increase of the content of achiral banana-shaped molecules. This characteristic effect in the chiral nematic field seems to offer the rational evidence for the twist conformation of such banana-shaped molecules, since the chirality should be included intrinsically within each chain. The asymmetric twist conformation in the ester linkage group connecting the central core with the side wings is likely to be the origin of enhanced twisting power.

Journal Article↗

PubMed2002

Fibroblast adhesion and proliferation on poly(ethylene glycol) hydrogels crosslinked by hydrolyzable polyrotaxane.

Fibroblast culture was performed to evaluate cell adhesion and proliferation on poly(ethylene glycol) (PEG) hydrogels crosslinked by a hydrolyzable polyrotaxane. The polyrotaxane consisting of alpha-cyclodextrins (alpha-CDs) and PEG terminated by benzyloxycarbonyl (Z)-L-phenylalanine (L-Phe) via ester linkage was used as a multi-functional crosslinker in the PEG hydrogels. From the results of contact angle and small angle light scattering measurements, it was suggested that the surface and bulk structure of the PEG hydrogels were heterogeneous. Fibroblast adhesion and proliferation on the hydrogels was observed. The number of fibroblast adhesion on the hydrogels crosslinked by the polyrotaxane was proportional to contact angle values and correlation length, and was significantly higher than those crosslinked by alpha-CDs in spite of similar contact angle and correlation length. These findings suggest that the cells recognize the surface heterogeneity due to the polyrotaxane structure, and the number of cell adhesion and proliferation is controllable by the polyrotaxane content in feed.

3T3 Cells↗

PubMed2002

Protein adsorption-resistant hollow fibers for blood purification.

Nonfouling polysulfone (PSf) hollow fiber membranes resistant to protein adsorption and deposition were newly developed by the addition of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer. To improve hydrophilicity, permeability, and nonfouling characteristics of the PSf hollow fiber in a hemodialyzer, we synthesized a MPC polymer which can be blended with PSf for preparing the polymer alloy (PSf/MPC polymer). The composition of the MPC polymer blended in the PSf was in the range between 7.0 and 15 wt%. From the PSf/MPC polymer solution, flat membranes and hollow fibers could be prepared. These membranes took an asymmetric structure, and its mechanical strength was good. The surface characterization of the PSf/MPC polymer hollow fiber membrane by X-ray photoelectron spectroscopy revealed that the MPC units were concentrated at the surface. The permeability for solutes through the PSf/MPC polymer membrane was higher, and the amount of protein adsorbed on the PSf/MPC polymer membrane was lower than those of the PSf membrane. Moreover, platelet adhesion was also effectively inhibited on the PSf/MPC polymer membrane.

Adsorption↗

PubMed2002

pH-modulated release of insulin entrapped in a spontaneously formed hydrogel system composed of two water-soluble phospholipid polymers.

To develop a polypeptide drug carrier through oral administration, a polymer hydrogel has been found that is very easy to prepare by mixing two water-soluble phospholipid polymers. The polymers having 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties spontaneously formed a hydrogel, which showed controllable dissociation via pH changes. In this study, the MPC polymer hydrogel was prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB), and the applicability of the hydrogel as an oral drug delivery carrier was examined. The gelation process from the two MPC polymers is spontaneous, requiring no chemical reactions and/or no physical stimuli. PMB has a hydrophobic domain, which is suitable for loading hydrophobic drugs. Insulin could be very easily loaded to almost 100% in the hydrogel. PMA also has carboxyl groups, which are well known for pH sensitivity. At pH 1.8, the swelling continued for 8 h, with complete dissociation after 16 h. At pH 6.8, the hydrogel completely dissociated within 4 h. The hydrogel remained stable at pH 1.8 and released all the insulin at pH 6.8. The release rate was approximately four times faster at pH 6.8. After release, the insulin did not show any denaturing tendency.

Drug Delivery Systems↗

PubMedDate not supplied

Characterization of the spontaneously forming hydrogels composed of water-soluble phospholipid polymers.

Spontaneously forming hydrogels composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers, poly(MPC-co-methacrylic acid) (PMA), and poly(MPC-co-n-butyl methacrylate) (PMB) were examined. The MPC copolymer hydrogel was observed to have a spontaneous gelation property. To determine the properties of the hydrogels and why the gelation takes place, we have studied the properties of the hydrogels by scanning electron microscopy, X-ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC). The morphologies of the hydrogels were spongelike with a homogeneous structure. By XPS analysis in terms of the molecular distributions in the hydrogels, it was observed that a stabilization time was required for the hydrogel to undergo chain rearrangement. DSC thermograms of the hydrogels were different from their components, PMA and PMB. For the hydrogel, a crystallization peak around -30 degrees C was observed. This result indicated that some ordered structures existed in the hydrogels. To determine the role of the MPC groups, aqueous solutions of poly(methacrylic acid) (PMAc) and PMB were mixed. The mixture of PMAc-PMB turned into a sol state, and the sol state remained for a week. When the mixture was cooled, a very weak hydrogel was prepared. This result suggested that the MPC groups were the dominant unit for spontaneously forming the hydrogels.

Biocompatible Materials↗

PubMedDate not supplied

Stereocomplex formation by enantiomeric poly(lactic acid) graft-type phospholipid polymers for tissue engineering.

A porous scaffold as a cell-compatible material was designed and prepared using a phospholipid copolymer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC), n-butyl methacrylate, and enantiomeric macromonomers, the poly(L-lactic acid) (PLLA) macromonomer, and poly(D-lactic acid) (PDLA) macromonomer. On the basis of the wide-angle X-ray diffraction and differential scanning calorimetry measurements, the formation of a stereocomplex between the PLLA and PDLA segments of the copolymer was observed on the porous scaffold. The porous structure was prepared by a sodium chloride leaching technique, and the pore was linked to the scaffold. The pore size was confirmed by scanning electron microscopy and found to be ca. 200 microm. These observations suggest that the porous scaffold makes it possible to produce cell-compatible materials, which may involve the following advantages for tissue engineering: (i) cell compatibility using phospholipid copolymer, (ii) adequate cell adhesion by poly(lactic acid), and (iii) complete disappearance of scaffold by dissociation of stereocomplex. The cell experiment using the porous scaffold will be the next subject and reported in a forthcoming paper.

Biocompatible Materials↗

PubMedDate not supplied

Cell adhesion and morphology in porous scaffold based on enantiomeric poly(lactic acid) graft-type phospholipid polymers.

Poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) macromonomers were synthesized for preparation of a novel cytocompatible polymer. The cytocompatible polymer was composed of 2-methacryloyloxyethyl phosphorylcholine (MPC), n-butyl methacrylate (BMA), and the enantiomeric PLLA (or PDLA) macromonomer. The degree of polymerization of the lactic acid in the PLLA and PDLA segments was designed to be ca. 20. The copolymer-coated surface was analyzed with static contact angle by water. From the result, the PLLA (or PDLA) segment and MPC unit were located on the coated surface, and the monomer unit in the copolymer was reconstructed by contacting water. Fibroblast cell culture was performed to evaluate cell adhesion on the coated surface, and the cell morphology was observed. The number of cell adhesion is correlated with the PL(D)LA content, and the cell morphology is correlated with the MPC unit content. The porous scaffold was prepared by the formation of a stereocomplex between the PLLA and PDLA, and the cell adhesion and following cell intrusion was then evaluated. The fibroblast cells adhered on the surface and intruded into the scaffold through the connecting pores after 24 h. The cell morphology became round shape from spreading with the decreasing PLLA (or PDLA) content in the copolymer. It is considered that the change in the cell morphology would be induced by the MPC unit as cytocompatible unit. These findings suggest that the porous scaffold makes it possible to have cytocompatibility and to produce three-dimensional tissue regeneration.

Cell Adhesion↗

PubMedDate not supplied

Regulation of enzyme-substrate complexation by a substrate conjugated with a phospholipid polymer.

To recognize and control ligand-receptor interactions at the interface between cells and polymer materials, we investigated a model system with an enzyme and a substrate conjugated with a biocompatible phospholipid polymer in an aqueous medium. We explored the regulation of enzyme-substrate (ES) complexation using horseradish peroxidase (HRP) as the enzyme and 4-aminoantipyrine (AAP) and 3-(p-hydroxyphenyl) propionic acid (HPPA) as substrates. The phospholipid polymer (PMBN), composed of 2-methacryloyloxyethyl phosphorylcholine, n-butyl methacrylate, and p-nitrophenyloxycarbonyl poly(oxyethylene)methacrylate, was prepared and conjugated with AAP (PMBN-AAP conjugate). The formation and dissociation of the ES complex were investigated using capillary electrophoresis and fluorescence spectroscopy. In the chart of the capillary electrophoresis, a much longer retention time of HRP was observed in the PMBN-AAP conjugate-coated capillary compared with that in a nontreated capillary. The retention time was significantly longer in comparison with the case of a mixed solution of HRP and AAP. This result clearly shows that HRP forms an ES complex with the immobilized PMBN-AAP conjugate and that the addition of AAP to the medium inhibits the interactions between HRP and the PMBN-AAP conjugate. Though HRP forms an ES complex with both AAP and the PMBN-AAP conjugate, the ES complex with the PMBN-AAP conjugate was easily dissociated by addition of HPPA as an alternative substrate because HRP started to react with the HPPA immediately. However, the HRP that formed an ES complex with AAP fell behind in reacting with the HPPA. The activity of HRP was maintained at the initial level in the presence of the PMBN-AAP conjugate at 25 degrees C for 1 week. Additionally, even under H(2)O(2) conditions, HRP stored with the PMBN-AAP conjugate maintained 40% of the initial activity whereas HRP was deactivated within 6 h. This result indicates that the PMBN-AAP conjugate could block the active sites by formation of an ES complex. This is due to the formation of the ES complex, which retained the structure of HRP by blocking the active sites. On the basis of these results, we considered that the reversible attachment and detachment by PMBN conjugated with specific ligands from cellular receptors will be realized.

Electrophoresis, Capillary↗

PubMedDate not supplied

Cell engineering biointerface focusing on cytocompatibility using phospholipid polymer with an isomeric oligo(lactic acid) segment.

Initial contact between a biological environment and a biomaterial ultimately decides the in vivo performance. Therefore, the fabrication of a delicate biointerface is important because it can be utilized as a platform for novel biomaterials. For the preparation of advanced biomedical devices such as biochips, nanoparticles, and cell engineering devices, the surface properties may be modified by the design of polymeric biomaterials. Anomalous phospholipid polymers with an isomeric oligo(lactic acid) segment were designed and evaluated as a biointerface. The phospholipid polymer containing 2-methacryloyloxyethyl phosphorylcholine was easily copolymerized with isomeric oligo(lactic acid) macromonomers, and the obtained polymer could easily form thin coating membranes as biointerfaces. The oligo(lactic acid) involves three kinds of isomers: dl-, d-, and l-forms. The favorable characteristic on the surface provides regulation of cell-material interactions on the biointerface. The oligo(lactic acid) segment could form hydrophobic domains, which were considered to be located on the interface, to enhance protein adsorption and cell adhesion. The most favorable characteristics on the biointerface were dual functions of cytocompatibility by the phospholipid polymer and cell adhesion property by the oligo(lactic acid) segment. In this study, we focused on the biological responses such as protein adsorption and cell adhesion by change in the oligo(lactic acid) component. The cell viability on the confluent stage was evaluated in terms of metabolic activity.

Animals↗