Papers by Author: Toru Tonegawa

Abstract: Insulin delivery carriers using low crystalline porous zinc hydroxyapatite (ZnHAp) microparticles with different crystal sizes and novel formulation method of poly (lactic acid) (PLA) have been developed to achieve the sustained-release of insulin. The adsorption isotherm curves of insulin dissolved into acetic acid of pH4.5 onto ZnHAp nanocrystals show non-Langmuir type due to the dissolution of the ZnHAp microparticles; the adsorption amounts were increased with the increase of crystalline sizes. The PLA formulation, coating the outer layer of microparticles, showed the apparent reduction of initial burst for insulin. The amounts of initial release of insulin decreased with the increase of crystalline sizes of ZnHAp, which could be attributed to the different meso-porous structure depending on its crystal sizes.

Abstract: Hydroxyapatite (HAp) sensor, available for quartz crystal microbalance with dissipation (QCM-D) technique, has been fabricated by an electrophoretic deposition method. The method of re-usability of the sensor after adsorption of fibrinogen and the biological apatite (BAp) growth on the sensor with and without the adsorption of feral bovine serum (FBS) from 1.5 simulated body fluid were investigated. The re-usability of the sensor, cleaning with the combination of ammonia and hydrogen peroxide mixture and UV/ozone treatment, achieved ten times reuses. BAp was grown on the HAp surface but not on the gold surface at 37.5 oC for 40 hours. The viscoelastic property (DD/Df value) of the BAp layer on the HAp sensor showed harder than that of the protein adsorption films from FBS. The amount of the BAp grown on the HAp sensor adsorbed FBS is lower than that on the HAp sensor. The adsorption of FBS proteins on the HAp surface strongly inhibited the BAp growth.

Abstract: Real time adsorption behaviors of six proteins with different isoelectric points on hydroxyapatite (HAp) nanocrystal surfaces have been investigated by using HAp sensors for quartz crystal microbalance with dissipation technique (QCM-D). The dissipation (D)–frequency (f) plots clearly showed that the different types of protein adsorption behaviors; the D-f plots of acidic proteins lie on one straight line with a constant slope under all initial protein concentrations, while those of neutral and basic proteins lie on two straight lines with different slopes. The acidic proteins formed a monolayer, while the neutral and basic proteins could cause conformational changes with the adsorbed amount of proteins. The QCM-D technique with novel HAp nanocrystal sensor is useful for the liquid phase changes of proteins on the surface.

Abstract: The adsorption properties of metal ions containing hydroxyapatite (Ca10(PO4)6(OH)2, HAp) were elucidated for the development of protein drug carrier. As-prepared metal ion containing HAp nanocrystal showed plate-like morphology with 10-20nm in length and 5-10nm in width. The metal ion containing HAp microparticles had higher specific surface area than the HAp microparticle. The adsorption amount per unit area of HAp showed higher than those of metal ion containing HAp. The adsorption behavior followed the Langmuir curves for each protein, indicating the monolayer adsorption. The loaded amount of proteins could be one of the most important properties for the application of drug delivery carrier.

Abstract: Control of protein release without the initial burst from zinc containing hydroxyapatite porous microparticles (Zn-HAp) was investigated with a novel formulation method. The formulation method was a coat of polyL(L-lactide; PLA) on the microparticle with nano-thickness, which obviously suppressed the initial burst of protein release compared with the microparticles without the formulation, the coat of PLA. The HAp/PLA microparticle with 1-20μm of the size distribution was available for the drug delivery carrier of proteins without the degradation.

Abstract: The extent of osseous involvement, particularly spinal cord compression, is directly correlated with patient survival. To treat metastatic spine cancer, we have developed novel paclitaxel-loaded hydroxyapatite-alginate gels. In this study, an intraosseous spinal cancer model in rats was used to investigate the efficacy of local treatment. Ten rats were randomized into two groups, a local treatment group and a control group. Disease-free time and survival rate in the local treatment group were significantly longer in this model. (p<0.05)

Abstract: Hydroxyapatite (HAp) also shows the high absorption ability for proteins with low degradations. In this study, to modify the absorption ability and to obtain high surface area, metal ions (Zn, Mg, Fe) were introduced in preparing the HAp nanocrystals, and porous microparticles were subsequent fabricated by a spray drying method. HAp microparticles with Zn, Mg, Fe ions had a single phase of low crystalline HAp. The specific surface area of the HAp, Mg-HAp, Fe-HAp and Zn-HAp were 87, 150, 152, 167 m2/g, respectively. In the adsorption experiment of a lysozyme as a basic proteine, Zn-HAp showed the highest adsorption ability. On the other hand, the HAp microparticles witn metal ions showed higher adsorption ability for BSA as a acitic protein than pure HAp microparticles.