Authors: Toru Tonegawa, Toshiyuki Ikoma, Tomohiko Yoshioka, Kazuo Shinozaki, Nobutaka Hanagata, M. Tanaka
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.
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Authors: Toshiyuki Ikoma, Motohiro Tagaya, Toru Tonegawa, Mitsuhiro Okuda, Nobutaka Hanagata, Tomohiko Yoshioka, Dinko Chakarov, B. Kasemo, M. Tanaka
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.
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Authors: Tomohiko Yoshioka, Toshiyuki Ikoma, Akira Monkawa, Toru Tonegawa, Dinko Chakarov, B. Kasemo, Nobutaka Hanagata, M. Tanaka
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.
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Authors: Toru Tonegawa, Toshiyuki Ikoma, Tomohiko Yoshioka, Guo Ping Chen, Nobutaka Hanagata, M. Tanaka
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.
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Authors: Toru Tonegawa, Toshiyuki Ikoma, Guo Ping Chen, M. Tanaka
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.
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Authors: Tetsuya Abe, Masataka Sakane, Toshiyuki Ikoma, Toru Tonegawa, Tomonori Yoshioka, M. Tanaka, Naoyuki Ochiai
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)
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Authors: Toru Tonegawa, Toshiyuki Ikoma, Akira Monkawa, Guo Ping Chen, M. Tanaka
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.
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