Kobunshi - Vol. 59, No. 7 (July, 2010)

Hot Topics

Vol. 59, No. 7, July (2010)

Application for Ophthalmic Medications of Stimuli-Responsive Polymers
Fumitaka TASAKA
R&D Division, Santen Pharmaceutical Co., Ltd.

In general, bioavailability of drugs instilled into the eye is extremely low. Many approaches to improve the bioavailability have been examined over time. One of the successful approaches is the application of stimuli-responsive polymers to eye drops. Eye drops containing stimuli-responsive polymers, like Timoptolｒ®XE and Rysmon®TG ophthalmic solutions, are water-soluble sols before instillation. After instillation, the drug retention on the eye surface could be improved by gelating in response to ions in tear fluids or surface temperature of the eye. As a result, it became possible to show the effect equal to twice-daily instillation had been made it into a mainstream application currently used to treat glaucoma and ocular hypertension by once-daily instillation, and to improve patient’s QOL (Quality of Life) remarkably. PMF Preprints, Japan 2009, 18, 180.

Photo-nanocomposite Gels with Superior Properties Prepared by In-situ Photopolymerization in an Aqueous System
Kazutoshi HARAGUCHI and Tetsuo TAKADA
Kawamura Institute of Chemical Research
Photo-nanocomposite gels (photo-NC gels), with superior mechanical, optical, and thermosensitive properties, were synthesized by free-radical polymerization initiated by a photo-initiator and UV radiation under optimized conditions in an aqueous system. The organic (polymer)/inorganic (clay) network structure and the mechanism of formation were similar to those of normal NC gels prepared by thermal redox-initiated system. The resulting photo-NC gels exhibit very desirable mechanical properties, e.g., ultrahigh elongation and high tensile strength, and these properties can be varied over a wide range by controlling the clay content. Further, a number of outstanding characteristics were observed, including anti-fogging properties as a coating, thermosensitive sliding frictional behavior, flow control in microfluidic channels, formation of patterned NC gels by UV light, and cell harvesting without treatment by enzymes. Polymer Preprints, Japan 2009, 58, 4243.

Group 5 Metals As Unique Catalyst Components for Living Polymerization and Selective Trimerization of Ethylene
Kazushi MASHIMA
Graduate School of Engineering Science, Osaka University
Half-metallocene complexes of niobium and tantalum bearing a 1,3-diene ligand, Cp*MR2(h4-1,3-diene) (M = Nb and Ta) served, upon activation by MAO, as unique catalysts for the living polymerization of ethylene, leading to polyethylene with the narrowest polydispersity (Mw/Mn up to 1.05) reported yet. On changing the diene ligand to 1,4-diaza-1,3-diene, to introduce TaÑN bonds tolerant to the carbonyl group and incorporating MMA as an auxiliary ligand, the tantalum complexes, Cp*M(1,4-diaza-1,3-diene)(h4-MMA), became catalysts for the living polymerization of MMA. In addition to these living polymerizations, ethylene oligomerization was catalyzed by low valent tantalum species to selectively give 1-hexene. Direct observation of metallacyclopentane confirmed that such the selective trimerization of ethylene was achieved proceeding via the metallacycle mechanism. Polymer Preprints, Japan 2010, 59, 52.

Inhomogeneity-free Tetra-PEG Gels as Revealed by Small-angle Neutron Scattering
Mitsuhiro SHIBAYAMA
Institute for Solid State Physics, The University of Tokyo
The structure of a series of polymer networks consisting of polyethylene glycol (PEG), Tetra-PEG, has been investigated by small-angle neutron scattering (SANS). The Tetra-PEG gels were prepared by cross-end coupling of two types of tetra-arm PEG macromers with the molecular weights, Mw, of 5, 10, 20 and 40 ´ 103 g/mol. The structure factors of both as- prepared and swollen gels were represented by Ornstein-Zernike (OZ) type scattering functions and could be superimposed to a single master curve with the reduced variables, xq and I(q)/f0x2, irrespective of the molecular weight of tetra-PEG, where q, x, I(q), and f0 are the magnitude of the scattering vector, the correlation length, the scattering intensity, and the polymer volume fraction at preparation, respectively. The SANS curves for swollen gels were independent of f0, indicating that Tetra-PEG gels are entanglement-free model networks. Polymer Preprints, Japan 2009, 58, 3526.

Side-Group and Solvent Dependent Chain Stiffness of Amylose Carbamates
Ken TERAO
Graduate School of Science, Osaka University
Dimensional and hydrodynamic properties of amylose tris(3,5-dimethylphenylcarbamate) (ADMPC), which is widely used as a chiral stationary phase, has been analyzed in terms of the wormlike chain mainly to determine the Kuhn segment lengths l-1 (chain stiffness parameter) in methyl acetate, 2-butanone, and 4-methyl-2- pentanone. The obtained l-1 is much higher than that for amylose tris(phenylcarbamate) in the same solvent [Biopolymers 2009, 91, 729], indicating that the slightly larger side group significantly stiffens the main chain. Furthermore, l-1 increases with an increase of molar volume of the solvent and reaches 73 nm in 4-methyl-2-pentanone, which is the highest value for previously investigated phenylcarbamate derivatives of polysaccharides. This high stiffness is most likely due to the steric hindrance of solvent molecules hydrogen-bonding to the NH groups of ADMPC. Polymer Preprints, Japan 2009, 58, 5241.

Simple Polyion Complex Hydrogel by Poly(acrylic acid) and Partially Protected Poly(vinylamine)
Hiroharu AJIRO, Yukie TAKEMOTO, Taka-aki ASOH, and Mitsuru AKASHI
The Center for Advanced Medical Engineering and Informatics, Osaka University
Poly(vinylamine) (PVAm) is the simplest polycation, which possesses a primary amine with high amount of nitrogen, so it is expected to be applied as effective functional material. N-vinylacetamide and N-vinylformamide, which are non-conjugate vinyl monomers, have been used as precursors, because their polymers give PVAm upon hydrolysis. We recently employed the interpenetrating polymer network for poly(N-vinylamides), in order to mix it with any monomers, such as poly(acrylic acid), a simple polyanion. Since there is no need to copolymerize, the anionic and the protected cationic moieties can be easily combined in hydrogel. After the preparation of an interpenetrating polymer network with poly(N-vinylamides) and poly (acrylic acid), we succeeded in the formation of a polyion complex at any desirable amount and position, such as the surface part of the hydrogel, which acts as a stimuli responsive drug release hydrogel with a stable swelling ratio. Polymer Preprints, Japan 2009, 58, 4281.

Shear-Quench Induced Discontinuous Growth Kinetics of Onion Structure
Shuji FUJII
Department of Chemistry, Nagaoka University of Technology, Japan
The radius of the onion structure reversibly changes with the applied shear rate. However, it is still controversial how the onion radius increased when the shear rate is reduced. We show in this paper that the kinetic of the onion growth is continuous with a slight quench of the shear rate but could be discontinuous when the shear rate is quenched below a threshold shear rate. In the discontinuous growth process, the smaller sized onion structure is once collapsed and forms planar lamellae, which transforms back to the large onion structure again under shear. Threshold shear rate is determined by the bending modulus of bilayers inside the onion structure. Prog. Colloid Polym. Sci. 2009, 136, 69. Polymer Preprints, Japan 2008, 57, 3780.

Supramolecular Nanotubes with a One-Dimensional Confinement Nanospace for Biomacromolecules
Naohiro KAMETA
Nanotube Research Center, National Institute of Advanced Industrial Science and Technology (AIST)
Rationally designed asymmetric amphiphiles self-assemble in water to produce molecular monolayer nanotubes with a well-defined size-dimension and functional inner and outer surfaces. The nanotubes provide a one-dimensional hollow cylinder that functions as a nano-container or -channel to encapsulate, transport, or release proteins and DNAs. The confinement effect, which depends on the size balance between the nanotube inner diameter and the guest proteins, allows the nanotube to stably storage those guests while keeping the active state under harsh conditions of temperatures and denaturant concentrations. Thus, supramolecular nanotubes can be expected to be applied as novel soft materials useful in biological and medical fields. Polymer Preprints, Japan 2009, 58, 2852. Chem. Mater. 2009, 21, 5892.

Development of Cationic Poly(amino acid)s for Safe and Efficient Polyion Complex-based Nucleic Acids Delivery
Kanjiro MIYATA
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
Fine-tuning of polycation structures drastically improves nucleic acids delivery with polycation/nucleic acids-based polyion complexes (PICs). In this study, environment-sensitive cationic poly(amino acid)s were designed for the preparation of smart PICs towards safe and efficient transfection. To achieve high complex stability in extracellular media and smooth release of nucleic acids in cell interior, thiol-installed poly(amino acid)s were prepared to form disulfide crosslinked PICs for intracellular reductive environment-selective release of nucleic acids. To develop PICs exerting efficient endosomal escape, poly(amino acid)s possessing ethylenediamine side chains were synthesized to facilitate the protonation in acidic endosomes and disrupt the endosomal membrane. Poly(ethylene glycol) (PEG)- or silica-coating of PICs was further performed for biocompatibility, rendering the PICs a promising candidate for successful gene therapy. Polymer Preprints, Japan 2010, 59, 1966.