Hiroki Katono

THERMO-RESPONSIVE SWELLING AND DRUG RELEASE SWITCHING OF INTERPENETRATING POLYMER NETWORKS COMPOSED OF POLY(ACRYLAMIDE-CO-BUTYL METHACRYLATE) AND POLY(ACRYLIC ACID)

Abstract The swelling behaviour of interpenetrating polymer networks (IPN) composed of poly (acrylic acid) (PAAc) and poly (acrylamide(AAm)-co-butyl methacrylate (BMA)) in water was studied and compared to crosslinked poly(AAm-co-BMA) and crosslinked poly(AAm-co-AAc-co-BMA). The IPNs were prepared by a sequential IPN method in which crosslinked PAAc chains were formed inside of three-dimensional networks ofpoly(AAm-co-BMA) as initial gels. Crosslinked poly(AAcco-AAm-co-BMA) gels (random gels) were also synthesized with the same monomer compositions as the IPNs to elucidate the effect of gel first-order structure on swelling behaviour. Positive swelling changes, i.e. lower swelling ratio at lower temperature and higher swelling ratio at higher temperature, were observed with temperature changes for both the IPNs and the random gels, while no change in swelling was observed for crosslinked poly(AAm-co-BMA) without AAc. In particular, IPN swelling showed a transition point at a certain temperature as a function of temperature change, while random gels showed simple and dull swelling changes with temperature change. The transition temperature of the IPNs shifts to higher temperature with increasing BMA content in IPNs. The positive temperature dependence is suggested to be linked to the formation and dissociation of hydrogen-bond complexes between AAc and AAm with temperature changes in IPNs and random gels. The observed transition in swelling changes in the IPN series is hypothesized to result from concurrent dissociation of continuous ladder-like polymer complexes between PAAc and PAAm matrices in the IPN. The shift of transition temperature induced by incorporation of BMA was due to the stabilization of the complex at higher temperature by increasing hydrophobic interactions. Reversible swelling changes, i.e. higher swelling ratio at high temperature (20°C, 30 °C, 40 °C) and lower swelling ratio at 10°C, in response to step-wise temperature changes between low and high temperature, were observed only for BMA-incorporated IPNs, while irreversible swelling was observed for IPNs without BMA. This result suggests that the presence of hydrophobic BMA had an important role in reversible swelling change of IPNs in response to temperature change. To evaluate the feasibility of IPNs for drug delivery systems, the release of ketoprofen from IPNs was performed with fluctuation of temperature between 10°C and 30 °C. The release rate of drug was reduced at 10°C, while it was increased at 30 °C. The difference of release rate between 10°C and 30 °C was considered to be due to different drug diffusivities between the temperatures induced by swelling changes of IPNs.

Novel Design of Microreservoir-Dispersed Matrices for Drug Delivery Formulations: Drug Release from Polybutadiene- and Poly (ethylene oxide)-Based Segmented Polyurethanes in Relation to Their Microdomain Structures

Drug release from monolithic devices of segmented polyether-poly- (urethane-urea) (PEUU)s based on 1,2-polybutadiene (PBD) and poly(ethylene oxide) (PEO) as their soft segments was examined in relation to their micro domain structures. Physical characterization of these PEUU films was carried out in terms of their thermal properties, dynamic mechanical properties, and water structure in water swollen PEUU films. These results reveal that the ter nary microdomain structures are composed of PBD, PEO, and hard segments. The drug release profiles of these PEUU devices are strongly affected by the physicochemical nature of soft segment matrices in PEUUs. The PEUUs with high PEO content exhibited slow and steady (zero-ordered) release of drug in contrast with those with low PEO content from which drug release was en tirely restricted. This result indicates the importance of a matrix to perform the function not only as a drug reservoir but also a transport channel. The solu bility parameters of both constituent segments and the drug must be realized for regulated drug release from microdomain-structured polymeric devices.

Introduction of Cu(II) complex into transparent synthetic resin and optical function of the resin as a near‐infrared ray cutoff filter

A mole ratio method was conducted to determine a necessary condition to solubilize Cu(II) ion into an organic solvent. Copper benzoate anhydrous (CB) and acetone was used as a Cu(II) ion supplier and a solvent, respectively. Methacryloyloxy-ethyl phosphate (PMOE) and di(2-ethylhexyl) phosphate (DIEHP) were used asligands for solubilization. Cu(II) ion was solubilized with only two PMOE molecules, although six molecules were needed for DIEHP. PMOE formed an intermediate layer which surrounded the Cu(II) ion with two molecules between the ion and solvent and made it possible to solubilize Cu(II) ion into the organic solvent. In the case of DIEHP, however, six molecules were needed to form such a layer for solubilization. Furthermore, Cu(II) ion was introduced homogeneously into poly(methyl methacrylate) (PMMA) by copolymerization of PMOE with MMA, although the polymer was opaque in the case of DIEHP. The ligand having a methacryloyl group was considered to participate in the polymerization process, which avoided exclusion of the Cu(II) complex from polymer phase. The intermediate zone formed by PMOE was considered to keep compatibility of Cu(II) ion with the polymer matrix even after polymerization. The near-infrared ray cutting-off filter made of resin was realized by introducing Cu(II) ion at higher concentration through complexation with the proper ligand.

Solid State Imaging Techniques. The Development of a Luminous Efficiency Plastic Filter Combined with Optical Low-pass Function.

We developed an unprecedented optical filter which has a luminous efficiency filtering function and an optical low pass filtering function for the downsizing of CCD camera optics. The filter was made of synthetic resin and it had phase grating on its surface. The light transmittance and the optical low-pass function of the new filter which had a 1 mm thickness were a little different from those of a conventional quartz device which had a thickness of more than 3 mm. We discuss the characteristics of and the production processes for the developed filter in this paper.

Control of Optical Properties of Cu(II) Complexes Formed with Phosphate Ligands in Transparent Resin and Applications to Near Infrared Ray Cut-Off Filter Containing the Complex.

リン酸メタクリロイルオキシエチル (PMOE) -銅イオン錯体のポリメチルメタクリレート中での近赤外光吸収特性と配位状態の関連性をモル比法によって考察し, この錯体を含有する樹脂板の吸収波長域の調整がモル比の調節によって可能であることを示した. ポリマー中の銅錯体の吸収ピーク波長 (λmax) は, モル比 [リン酸エステル中リン酸基のOH] / [Cu2+] が2から6の範囲で800から840nmヘシフトし, 6以上では一定値840nm付近を示した. [OH] / [Cu2+] =2ではメタクリロイル基中のCOO基も配位しているが, 2から6の間でのλmaxが変化することと6以上で一定であることから, POH基濃度増大に従いCOO基からPOH基への逐次配位置換反応が起きたと推測された. 6以上では置換反応は起こっておらず, POH基6配位状態で安定化していることがわかった. また, 上述のモル比とλmaxの関係を用いることによりこの錯体を含有する近赤外線カットフィルターの可視光透過域/近赤外線カット域の境界波長のコントロールが可能となった.

Near Infrared Ray Cut-Off Function of Optical Filter Made of Synthetic Resin Containing Cu(II) Complex Formed with Phosphoric Acid Ester.

安息香酸銅 (無水) はメチルメタクリレート (MMA) 中において2量体構造で存在しMMAには難溶な物質であるが, 銅錯体形成の配位子としてリン酸エステルを用いることにより, 銅イオンは単量体構造を有する錯体を形成して可溶化することがわかった. この単量体錯体は840nm付近に吸収ピークを有する700～1500nmのブロードな吸収を示す光学特性を有することがわかった. 重合性官能基を有するリン酸エステルを用いることによりMMAと共重合させることが可能となり, 銅錯体をポリメチルメタクリレート (PMMA) に均一に導入することが可能となった. この光学特性を有する銅錯体を導入することにより, 実用性の高い近赤外線カット機能を有するプラスチック製フィルターを実現することができた.

Optical Plastic Filter Containing Copper Benzoate(II).

メタクリル酸メチル (MMA) に難溶な無水安息香酸銅 (CB) はメタクリル酸 (MAAc) の共存下においてその溶解性が向上する. CBはMMA中では2量体構造をとるが, 2量体CBの二つのアピカル位にMAAcが1個ずつ配位することがわかった. このMAAcの配位によりCBのMMAへの親和性が増大し, 可溶化したと考えられる. MAAcを配位させたCBと高分子マトリックス形成用のモノマーとを共重合させることによって, 銅を含有する透明なプラスチック製近赤外線カットフィルターが得られた. このフィルターは, 厚さ0.5mmの薄さでも600～800nmの範囲で透過率がほぼ0%の近赤外線カット性を示した.

Molecular Design of Novel Thermo-responsive Hydrogel Membranes and Their Applications.

Molecular design of thermo-sensitive hydrogels was discussed. Interpenetrating polymer networks (IPNs) composed of poly (acrylamide (AAm)-co-butyl methacrylate (BMA)) have been investigated in terms of temperature dependence of swelling and their application to thermo-responsive drug delivery. PAAm and PAAc formed polymer complex at lower temperature by hydrogen bonding, and the complex dissociated at above a certain temperature at which the complex initiated dissociation all at once due to zipper effect. The IPNs showed lower swelling at lower temperatures and higher swelling at higher temperatures due to complex formation/dissociation change, exhibiting drastic change at around 25°C due to the zipper effect. However, the temperature, 25°C, is too low to apply to practical use. To shift the temperature to body temperature, poly (N-acrylylglycinamide) (PAG) was used instead of PAAm. AG has two amide groups in the side chain, which was considered to strengthen stability of polymer complex by hydrogen bond with PAAc. The IPN composed of PAG and PAAc actually demonstrated swelling/shrinking change at around 40°C. N, N-dimethylacrylamide (DMAAm) was also used for the same purpose with AG. DMAAm is a strong acceptor for hydrogen bonding. Incorporation of DMAAm into PAAm strengthened stability of PAAm/PAAc complex, and shifted the changing temperature of formation/dissociation to higher. In conclusion, the switching temperature of ON-OFF drug release could be controlled by proper molecular design of complexation sites of hydrogen bonding polymer complex.