Biomedical subjects

Madoka Takai

Publications and source records attributed to Madoka Takai.

13 recordsLinked to original sources

PubMed2007

Biocompatibility and drug release behavior of spontaneously formed phospholipid polymer hydrogels.

Hydrogels containing 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties were formed from aqueous solutions with water-soluble MPC polymers with carboxylic acid and alkyl groups because of hydrogen bonding formation. To investigate the biocompatibility and drug release behavior of the hydrogels, we used random- and block-type carboxylic acid MPC polymers, such as poly [MPC-co-methacrylic acid (MA)] (rPMA), poly[MPC-co-4-(2-methacryloyloxyethyl) trimellitic acid (MET)] (rPMT), poly (MA-block-MPC-block-MA) (bPMA) and poly(MET-block-MPC-block-MET) (bPMT), and alkyl MPC polymers, such as poly[MPC-co-n-butyl methacrylate] (PMB) and poly(MPC-co-benzyl methacrylate) (PMBz). We investigated the biocompatibility of the spontaneously formed MPC polymer hydrogels by a hemolysis test and an in vivo injection test. The random MPC polymers having carboxylic acid groups expressed more hemolytic activity compared to the block polymers. The results of the in vivo injection test also indicated low biocompatibility of the carboxylic acid polymers especially at high concentration. The alkyl MPC polymers, the PMB and PMBz showed excellent biocompatibility in both hemolysis and in vivo injection test. However, the hydrogels, the rPMA/PMB hydrogel (rABgel) and the rPMT/PMBz hydrogel (rTZgel) lowered the hemolytic activity of elemental polymers, the rPMA and rPMT. Thus, suppression of the ionization of the carboxylic acid groups is necessary for biocompatibility. We also investigated the drug release behavior with attention to the interaction between the polymer and the drugs. The release behavior of a relatively low-molecular-weight hydrophilic drug, 5-fluorouracil, did not depend on the structure of the polymers. The higher-molecular-weight drugs, ketoprofen and indomethacin, were released faster from the block polymer hydrogel than the random polymer hydrogel, the rABgel, while the highest-molecular-weight drug, doxorubicin, was released faster from the random polymer hydrogel. A probable reason for this is the difference in the molecular structure; that is, the separated hydrophilic and hydrophobic sections in the block polymers constructed pathways where a drug can diffuse. In addition, the rTZgel suppressed the release of a drug with a large number of aromatic rings probably because of the stacking effect. The results of the compression test also suggested the existence of the stacking effect between the rTZgel and the drugs. Based on these results, control of drug release is possible by selecting a reservoir with an appropriate chemical structure to interact with the drug. For example, release of a relatively linear-structured drug with less aromatic rings can be suppressed in the rABgel rather than in the rTZgel. Thus, it can be concluded that if the ionization is suppressed, these MPC polymer hydrogels can be used as a material for a drug reservoir that can be selected according to the drug.

Animals↗

PubMed2006

Antibody immobilization to phospholipid polymer layer on gold substrate of quartz crystal microbalance immunosensor.

To modify gold electrode for immunosensor to construct an artificial cell membrane structure, water-soluble amphiphilic phospholipid polymer, poly[2-methacryloyloxyehtyl phosphorylcholine-co-n-butyl methacrylate-co-p-nitrophenyloxycarbonyl poly(ethylene glycol) methacrylate (PMBN)] was applied. The polymer had active ester groups for immobilization of biomolecules and it was converted partially to thiol groups for binding to gold substrates. The partially thiolated PMBN was adsorbed on a gold electrode of quartz crystal microbalance (QCM). Surface characterization of adsorbed PMBN layers was thoroughly investigated with reflectance anisotropy spectroscopy, ellipsometry spectroscopy, dynamic contact angle and X-ray photoelectron spectroscopy measurements. Among several PMBN, having different degree of thiolation, it was concluded that 21.5% thiolated PMBN layer had the most well-ordered phosphorylcholine groups in its outer surface. The proteins adsorption test revealed that the phosphorylcholine group on the outer side of PMBN layers, which was substituted their active ester groups by glycine, showed suppress the non-specific adsorption of proteins, such as bovine serum albumin and gamma-globulin. Also, through antigen-antibody binding evaluation, the anti-C-reactive protein antibody immobilized on the PMBN surface worked well and it was confirmed that denaturation of the antibody on the PMBN layers was hardly occurred in spite of 60 days storage at 4 degrees C. The antibody conjugated phospholipid polymer layer with well-ordered phosphorylcholine group could be outstanding functional membrane for biomedical diagnostic devices without non-specific binding and reduction of immunologic activity of immobilized antibody.

Antibodies↗

PubMed2006

Surface modification on microfluidic devices with 2-methacryloyloxyethyl phosphorylcholine polymers for reducing unfavorable protein adsorption.

Surface modification of polymer materials for preparing microfluidic devices including poly(dimethyl siloxane) (PDMS) was investigated with phospholipids polymers such as poly(2-methacryloyloxylethyl phosphorylcholine(MPC)-co-n-butyl methacrylate) (PMB) and poly(MPC-co-2-ethylhexyl methacrylate-co-2-(N,N-dimethylamino)ethyl methacrylate) (PMED). The hydrophilicity of every surface on the polymer materials modified with these MPC polymers increased and the value of zeta-potential became close to zero. The protein adsorption on the polymer materials with and without the surface modification was evaluated using a protein mixture of human plasma fibrinogen and serum albumin. Amount of proteins adsorbed on these polymeric materials showed significant reduction by the surface modification with the MPC polymers compared to the uncoated surfaces ranging from 56 to 90%. Furthermore, we successfully prepared PDMS-based microchannel which was modified by simple coating with the PMB and PMED. The modified microchannel also revealed a significant reduction of adsorption of serum albumin. We conclude that the MPC polymers are useful for reducing unfavorable protein adsorption on microfluidic devices.

Adsorption↗

PubMed2006

Photoinduced phospholipid polymer grafting on Parylene film: advanced lubrication and antibiofouling properties.

Poly(p-xylylene) (Parylene C) coatings have been applied in implantable electronic devices because of their electrical insulation and moisture barrier properties. To provide lubrication and an antibiofouling surface, a biomimetic phospholipid polymer--poly(2-methacryloyloxyethyl phosphorylcholine (MPC))--was grafted from the surface using UV irradiation with benzophenone as an initiator. The poly(MPC) grafting on the Parylene C films was confirmed by attenuated total reflection-Fourier transfer inflated irradiation, X-ray photoelectron spectroscopy and ellipsometry. These analyses indicated that the Parylene C films were completely covered by the poly(MPC)-graft layer with an average thickness of 140 nm under dry condition. The atomic force microscope (AFM) images revealed that the poly(MPC)-graft chains extended under wet condition. However, they formed globular structures under dry condition. Water contact angle measurements revealed a decreased receding angle of 29.5 degrees on the poly(MPC)-grafted surface with a high hysteresis of 41.4 degrees. These results indicate that the poly(MPC)-graft chains gain mobility in a wet environment. The average kinetic friction coefficient of the poly(MPC)-grafted surface in water was 0.018, which was 90% lower than that of the original surface. The in vitro single protein adsorption reduced by over 70% due to the poly(MPC) grafting. The hydrated poly(MPC)-graft chains are considered to provide lubrication and antibiofouling properties. The surface zeta potential measurement clarified the electroneutrality of the poly(MPC)-grafted surface. We concluded that the poly(MPC) grafting from the Parylene C layer significantly improved its surface properties and, subsequently, its biological properties.

Animals↗

PubMed2006

Maskless microfabrication of thermosensitive gels using a microscope and application to a controlled release microchip.

Here we show a simple and convenient method to prepare micropatterned gels by the use of a microscope, without large-scale or special-order experimental setup. UV light focused by an objective lens was locally irradiated to a pre-gel solution in a microchannel. This method would be useful for preparing microgels at target positions in microchips. A controlled drug-release microchip has actually been fabricated by utilizing this local photo-irradiation method, and pulsatile drug release in response to temperature changes was demonstrated.

Journal Article↗

PubMed2006

Biomimetic phosphorylcholine polymer grafting from polydimethylsiloxane surface using photo-induced polymerization.

The biomimetic synthetic phospholipid polymer containing a phosphorylcholine group, 2-methacryloyloxyethyl phosphorylcholine (MPC), has improved the surface property of biomaterials. Both hydrophilic and anti-biofouling surfaces were prepared on polydimethylsiloxane (PDMS) with MPC grafted by surface-initiated photo-induced radical polymerization. Benzophenone was used as the photoinitiator. The quantity of the adsorbed initiator on PDMS was determined by UV absorption and ellipsometry. The poly(MPC)-grafted PDMS surfaces were characterized by XPS, ATR-FTIR and static water contact angle (SCA) measurements. The SCA on PDMS decreased from 115 degrees to 25 degrees after the poly(MPC) grafting. The in vitro single protein adsorption on the poly(MPC)-grafted PDMS decreased 50-75% compared to the unmodified PDMS. The surface friction of the poly(MPC)-grafted PDMS was lower than the unmodified PDMS under wet conditions. The oxygen permeability of the poly(MPC)-grafted PDMS was as high as the unmodified PDMS. The tensile property of PDMS was maintained at about 90% of the ultimate stress and strain after the poly(MPC) grafting. The surface-modified PDMS is expected to be a novel medical elastomer which possesses an excellent surface hydrophilicity, anti-biofouling property, oxygen permeability and tensile property.

Biomimetic Materials↗

PubMed2006

Dual mode bioreactions on polymer nanoparticles covered with phosphorylcholine group.

We investigated the preparation of polymer nanoparticles covered with phosphorylcholine (PC) groups and the immobilization of proteins in order to observe dual mode bioreactions on the nanoparticles. For the surface modification on the nanoparticles, a water-soluble amphiphilic phospholipid polymer with PC groups as a hydrophilic moiety was synthesized. In this polymer, an active ester group, which can immobilize proteins, was introduced. Using the phospholipid polymer as a solubilizer, poly(L-lactic acid) nanoparticles were prepared from its methylene chloride solution in an aqueous medium by the solvent evaporation method. The diameter of the nanoparticles was ca. 200 nm and the surface was covered with the PC groups and active ester groups. Proteins could immobilize on the nanoparticles under mild conditions by the reaction between the active ester group and amino group in the proteins. Both an antibody and enzyme were immobilized on the nanoparticles and bioreactions such as the antigen/antibody reaction and enzymatic reaction were observed. When an antigen was added to the suspension of the nanoparticles, aggregation of the nanoparticles occurred and then they precipitated. Also, the enzymatic reaction proceeded well when the enzyme substrate was added to the suspension. Based on these results, we provided polymer nanoparticles functionalized with both the antibody and enzyme, and the dual mode bioreactions could occur. We concluded that the novel polymer nanoparticles could be used for nano-/micro-scaled diagnostic and medical treatment systems.

Antibodies, Monoclonal↗

PubMed2006

Asymmetrically functional surface properties on biocompatible phospholipid polymer membrane for bioartificial kidney.

To obtain a bioartificial kidney composed of a porous polymer membrane and renal cells, a polysulfone (PSf) membrane (PSM) blended with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was prepared. The PSM flat membrane with a porous structure could be prepared from the polymer blend containing 1 wt % of the MPC polymer in PSf by the phase inversion technique in a dry-wet process. Asymmetrical surface properties were observed on both sides of the membrane surfaces. That is, the sponge layer formed at the substrate-contacting surface of the membrane had 10-20 microm pores, but the pores in the micrometer range could not be observed for a skin layer formed at the air-contacting surface of the membrane. At the sponge layer surface, the MPC unit composition was 7 times larger than that at the skin layer surface. The amount of proteins adsorbed on the surface corresponded to the MPC unit composition. On the skin layer, a small amount of adsorbed proteins and platelet adhesion could be suppressed compared with those on the sponge layer. However, the skin layer had a moderate protein adsorption, so it showed a sufficient cytocompatibility to enable renal tubule epithelial cells to adhere and proliferate in the membrane. Thus, it functioned well as a renal tubule. Therefore, because of both its hemocompatibility and cytocompatibility, we could conclude that the PSM membrane is useful for as a renal tubule device for a bioartificial kidney.

Adsorption↗

PubMed2005

Piezoelectric immunosensor for bisphenol A based on signal enhancing step with 2-methacrolyloxyethyl phosphorylcholine polymeric nanoparticle.

An immunoassay in which BPA competed with a BPA-horseradish peroxidase conjugate for binding to anti-BPA antibodies, coupled to a piezoelectric (PZ) immunosensor, was able to detect 0.1 ng mL(-1) BPA. To enhance the sensitivity of the assay, we tested nanoparticles approximately 200 nm in diameter, coupled to anti-BPA antibodies, to increase the mass change on the surface of the immunosensor and thereby increase the frequency shift detected. This second step, using nanoparticles coated with anti-BPA antibodies, improved the sensitivity of the assay by approximately eight times at BPA concentrations below 10 ng mL(-1). Field emission-scanning electron microscopy (FE-SEM) showed that polymeric 2-methacrolyloxyethyl phosphorylcholine (MPC) nanoparticles coupled to antibodies remained monodisperse on the surface of the immunosensor and therefore produced stable signals in the immunosensors. Since the frequency shift detected in the assay mainly originated from the mass change on the surface of the PZ crystal, the colloidal stability of the antibody-conjugated particles used in the enhancement step played an extremely important role in achieving a stable and highly sensitive signal.

Antibodies, Monoclonal↗

PubMed2005

High functional hollow fiber membrane modified with phospholipid polymers for a liver assist bioreactor.

For practical application of a liver assist system with a tissue-conjugated hollow fiber membrane (HFM) bioreactor used in an extracorporeal therapy, it would require a highly sophisticated HFM which has both hemocompatibility on one side and cytocompatibility on the other side. In this study, we present a cellulose acetate (CA) HFM modified with 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers (PMB30 (MPC-co-n-butyl methacrylate) and PMA30 (MPC-co-methacrylic acid) for preparing a novel liver assist HFM bioreactor. A CA/PMB-PMA30 HFM modified asymmetrically on the inner and outer surface with the PMB30 and PMA30 was prepared successfully. Analysis with an X-ray photoelectron spectroscope showed that the intensity of the phosphorus atom attributed to the MPC units on the outer surface of the modified HFM was stronger than that of the inner surface. The PMA30 was immobilized on the outer surface of the CA/PMB30 blend HFM by a chemical condensation reaction. The CA/PMB-PMA30 HFM showed good water and solute permeability in comparison with the CA HFM. The morphologies of the adherent hepatocytes were round in shape in comparison with the cells that adhered on CA HFM. Furthermore, hepatocytes cultured on the inner surface of the CA/PMB-PMA30 HFM showed higher functional expression in terms of urea synthesis and albumin synthesis than that of the CA HFM.

Animals↗

PubMed2005

Design of functional hollow fiber membranes modified with phospholipid polymers for application in total hemopurification system.

In this study, we prepared cellulose acetate (CA) hollow fiber membranes (HFMs) modified with poly (2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate)(PMB30 and PMB80) by the dry-jet wet spinning process. The physical and chemical structures of the HFMs were controlled in order to design highly functional HFMs that had suitable performance to each targeting HFM device used in a total hemopurification system. The CA HFMs modified with the MPC polymer, such as CA/PMB30, CA/PMB80, and CA/PMB30-80 HFMs, were successfully prepared by controlling the spinning conditions. The modified HFMs showed an improved performance in solute and water permeability, due to the modification by the hydrophilic MPC polymers. The CA/PMB30 and CA/PMB80 showed a high potential in an application for a high performance hemocompatible plasmapheresis and hemofilter device. Furthermore, CA/PMB30-80 HFM, modified asymmetrically with PMB30 and PMB80, showed a potential for application in an advanced total hemopurification system as a highly functional scaffold for a biohybrid renal tubule, or a liver assist bioreactor device, because of their enhanced permeability, hemocompatibility, and cytocompatibility.

Animals↗

PubMed2005

Spontaneously forming hydrogel from water-soluble random- and block-type phospholipid polymers.

The mixed aqueous solutions of two water-soluble phospholipid polymers, such as poly[2-methacryloyloxyethyl phosphorylcholine(MPC)-co-methacrylic acid(MA)] (rPMA) and poly[MPC-co-n-butyl methacrylate(BMA)] (PMB), spontaneously form a hydrogel at room temperature without any chemical treatment due to hydrogen bonding formation between the carboxyl groups. With the objective of enhancing the hydrogen bonding efficiency, we have focused on the density of the carboxyl groups by controlling the chemical structure and monomer unit sequence. Thus, a random and an ABA-block-type MPC copolymer having carboxylic acids, poly[MPC-co-4-(2-methacryloyloxyethyl) trimellitic acid(MET)] (rPMT) and poly(MA)-poly(MPC)-poly(MA) (bPMA), have been designed. The purpose of this study is to investigate the gelation mechanism and physical properties of a hydrogel composed of rPMA and PMB (ABgel), one of bPMA and PMB (bABgel), and one of rPMT and poly(MPC-co-benzyl methacrylate) (PMBz) (TZgel). The Raman spectroscopic analysis and the rheological study of the dissolution behaviors indicated that the TZgel formation occurred due to inter- and intra-molecular hydrogen bonding formation between the carboxyl groups in the rPMT. The gelation mechanism of the bABgel was investigated by the dynamic light scattering measurement, the scanning electron microscopy observation and the rheological study. The results showed that the bPMA chains aggregate in the aqueous medium and transform into a hydrogel network structure. The bPMA needed much more gelation time than the rPMA due to this transformation. There was no difference between the gelation periods of the ABgel and the TZgel. The compression strengths of the ABgel and the bABgel showed no significant difference, while that of TZgel was lower than ABgel. The reason for this is that the polymer chains and bulky side chains of rPMT inhibit rearranging into a planar conformation and forming hydrogen bondings. These results lead to the conclusion that the properties of these MPC polymer hydrogels can be controlled by not only the chemical structure of the polymer but also the monomer unit sequence containing carboxyl groups.

Biocompatible Materials↗

PubMed2004

Surface characteristics of block-type copolymer composed of semi-fluorinated and phospholipid segments synthesized by living radical polymerization.

A series of random and block copolymers composed of hydrophilic and hydrophobic monomer units have been synthesized by the free and living radical polymerization methods, respectively. The hydrophilic monomer unit, 2-methacryloyloxyethyl phosphorylcholine (MPC), was selected because the MPC polymers are well-known for their excellent bio- and blood compatibilities. The semi-fluorinated monomer, 2,2,2-trifluoroethyl methacrylate (TFEMA), was used as the hydrophobic monomer unit. Several analyses of the copolymer surface showed that the TFEMA unit was concentrated at the outermost surface on the random copolymer surface and characteristics of MPC unit was dominant on the block copolymer with a low-MPC-unit composition in the dry state. A reorientation of the MPC unit occurred dynamically in the wet state because of the strong hydrophilicity of the MPC units. In the case of the block copolymer with a low-MPC-unit composition, the surface was covered with the MPC units in the wet state. As a result, the amount of the adsorbed bovine plasma fibrinogen and bovine serum gamma-globulin on the block copolymer surface was reduced dramatically.

Adsorption↗