Yuji Shibasaki

Hyperbranched Double Hydrophilic Block Copolymer Micelles of Poly(ethylene oxide) and Polyglycerol for pH-Responsive Drug Delivery

We report the synthesis of a well-defined hyperbranched double hydrophilic block copolymer of poly(ethylene oxide)-hyperbranched-polyglycerol (PEO-hb-PG) to develop an efficient drug delivery system. In specific, we demonstrate the hyperbranched PEO-hb-PG can form a self-assembled micellar structure on conjugation with the hydrophobic anticancer agent doxorubicin, which is linked to the polymer by pH-sensitive hydrazone bonds, resulting in a pH-responsive controlled release of doxorubicin. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy demonstrated successful formation of the spherical core-shell type micelles with an average size of about 200 nm. Moreover, the pH-responsive release of doxorubicin and in vitro cytotoxicity studies revealed the controlled stimuli-responsive drug delivery system desirable for enhanced efficiency. Benefiting from many desirable features of hyperbranched double hydrophilic block copolymers such as enhanced biocompatibility, increased water solubility, and drug loading efficiency as well as improved clearance of the polymer after drug release, we believe that double hydrophilic block copolymer will provide a versatile platform to develop excellent drug delivery systems for effective treatment of cancer.

One-pot synthesis of linear-hyperbranched amphiphilic block copolymers based on polyglycerol derivatives and their micelles.

This paper describes the one-pot synthesis of a polyglycidol (PG)-based polymer, poly(ethoxyethyl glycidyl ether) (PEEGE)-b-[hyperbranched polyglycerol (hbPG)-co-PEEGE]x/y, its micelle formulation, and the ability to encapsulate a model therapeutic molecule. Amphiphilic block copolymers were prepared by the sequential addition of ethoxyethyl glycidyl ether (EEGE) to glycidol. The composition of the block copolymers varied from 62:38 to 92:8. Block copolymers with composition x:y≥66:34 were soluble only in organic solvents. Micelles were formulated by injection of deionized water into a tetrahydrofuran block copolymer solution with or without pyrene as a model hydrophobic molecule. The critical micelle concentration was 18.2-30.9 mg/L, and the micelle size was 100-250 nm. The pyrene-containing micelle rapidly collapsed on acidic exposure, allowing conversion of hydrophobic PEEGE to hydrophilic PG, thus, facilitating the release of the encapsulated pyrene. Cytotoxicity data showed high biocompatibility of PG-based block copolymers, suggesting their potential as a drug delivery carrier.

Surface Morphological Changes in Monolayers of Aromatic Polyamides Containing Various N-Alkyl Side Chains

We synthesized new aromatic polyamides (poly-(N-alkylated benzamides), abbrev. PABA(n)) having both a rigid main chain and a flexible side chain with different lengths. We investigated the solid-state structures, that is, the molecular orientation and surface morphology, of organized molecular films of PABA(n) by performing surface pressure-area (pi-A) isotherm, in-plane and out-of plane X-ray diffraction (XRD), polarized infrared spectroscopy, and atomic force microscopy (AFM) measurements. The solid-state structure of poly-(N-methyl benzamide) (PABA(1)) belonged to the monoclinic system, whereas PABA(3), PABA(4), and PABA(5) showed an orthorhombic packing pattern. PABA(7) and PABA(8) formed amorphous polymers. In the case of PABA(17), a two-dimensional hexagonal lattice was formed as a subcell consisting of side chains. These polymer monolayers were highly condensed on a water surface at 15 degrees C. Out-of-plane XRD measurement results showed that the PABA(1), PABA(3), PABA(4), and PABA(5) multilayers showed large periodicities of 50-60 A. From AFM observation results, it was found that these aromatic polyamides formed single particle layers of hydrophilic groups localized at the bottom of the particles. On the other hand, PABA(7) and PABA(8) monolayers showed irregularity and exhibited shapeless morphologies. In addition, an organized molecular film of PABA(17) formed a highly ordered layer structure (periodicity of 30 A) and a giant circular domain (diameter of 20 nm) made of a side chain crystal. The PABA(17) monolayer showed a hexagonal packing pattern formed due to van der Waals interaction between the flexible side chains. From these experimental findings, it was concluded that the polymer synthesis method employed in the present study can be directly used to control the crystal structure (the third order structure of polymers), molecular arrangement, and surface morphologies of polymer monolayers.

Activated monomer cationic polymerization of 1,3‐dioxepan‐2‐one initiated by water‐hydrogen chloride

The ring-opening polymerization of 1,3-dioxepan-2-one (7CC) was carried out by water-hydrogen chloride as an initiator to obtain the corresponding polymer with the molecular weight controlled by the amount of water. A 1H NMR spectroscopic study suggests that the chain growth in this system is based on the attack of the terminal hydroxyl group to the monomer activated with hydrogen chloride.

Fabrication and structure of "polymer nanosphere multilayered organization".

We constructed a multiparticle layered organization of aromatic polyamides with rigid main chains and flexible side chains by the Langmuir-Blodgett (LB) technique, which resulted in a highly regular arrangement along the c-axis. The particle arrangement was estimated by performing out-of-plane X-ray diffraction (XRD) analysis and atomic force microscopic (AFM) observation. The results suggest that a double-particle layered structure (Y-type) is formed by the LB technique, forming amphiphilic particles at the air/water interface. Copolymers with highly hydrophobic carbazole contents and both hydrogenated and fluorinated side-chains also formed a single-particle layer at the air/water interface and exhibited multiparticle layers by a LB technique. Therefore, it is possible to control the formation of single- and double-particle layered structure using these techniques. Further, it was found that multiparticle layered organization of polymer nanospheres and polymer nanosheets could be formed simultaneously with the same component material.

Block copolymerization of tetrahydrofuran with δ-valerolactone by the samarium iodide-induced transformation

SummaryPolymerization behavior of δ-valerolactone (VL) with alkylsamarium (RSmI2) was studied, and its application to the block copolymerization of tetrahydrofuran (THF) with VL was examined. Polymerization of VL by butylsamarium gave the corresponding poly(VL) in good yield. The yield increased with increasing the concentration of VL and decreasing the polymerization temperature, resulting from the equilibrium between VL and poly(VL). The decrease in the molecular weight of poly(VL) by prolonging the polymerization time indicated the existence of back-biting reaction to form cyclic oligomers. The polymerization of VL with poly(THF)-macroanion obtained by the two-electron reduction of the propagation center of living poly(THF) with SmI2 led to the block copolymer of THF with VL. The initiation efficiency of VL-polymerization was almost quantitative, and the unit ratio of THF and VL-segments could be controlled by both the polymerization time of THF and the amounts of VL.

Crosslinked, Glassy Styrenic Surfactants Stabilize Quantum Dots Against Environmental Extremes.

Semiconductor, quantum dot (QD) nanoparticles (including CdSe/ZnS, CdTe/ZnS, and CdSe) were encapsulated within cross-linked shells of amphiphilic polystyrene-block-poly(acrylic acid) block copolymer. Transmission electron microscopy revealed that each particle was surrounded by a uniform, layer of copolymer, and that the average diameter of the resulting QD-core micelles was between 25 and 50 nm, depending on the conditions of particle assembly. Overall, we found that aqueous suspensions of these QDs were substantially more stable to heat and pH than particles with other surface preparations; we argue that the enhanced stability is due to the uniform, hydrophobic coating of polystyrene around each particle and the reinforcement of this layer by shell-cross-linking. The biocompatibility of these particles was investigated by microinjection of particle suspension into live zebrafish embryos. The particles permanently stained the fish vasculature, but did not interfere with the normal development of the fish. We propose that QDs encapsulated in cross-linked block-copolymer shells allow QDs to be used in biological or biotechnological protocols requiring harsh reaction conditions.

Transformation of the cationic growing center of poly(tetrahydrofuran) into an anionic one by bis(pentamethylcyclopentadienyl)samarium

Transformation of the cationic growing center of living poly(tetrahydrofuran) [poly(THF)] into an anionic one was achieved in high efficiency (62%) by the end-capping of living poly(THF) with potassium iodide followed by the reduction with bis(pentamethylcyclopentadienyl)samarium (Cp * 2 Sm), whereas the direct reduction with Cp * 2 Sm without the end-capping resulted in the formation of poly(THF) with pentamethylcyclopentadienyl group at the terminal. The increase in the molecular weight of poly(THF) after the reduction was observed, which indicates the presence of the dimerization of poly(THF) during the reduction. The polymerization of variety of electrophilic monomers including δ-valerolactone, 2-oxo-1,3-dioxane, and alkyl methacrylates with the macroanion provided good yields of the corresponding block copolymers consisting of both cationically and anionically polymerizable monomers.

Synthesis of highly refractive and highly fluorescent rigid cyanuryl polyimines with polycyclic aromatic hydrocarbon pendants

A series of rigid cyanuryl polyimines, polyguanamines (PGs) bearing polycyclic aromatic hydrocarbon pendants were successfully synthesized from 2-substituted 4,6-dichloro-1,3,5-triazine and aromatic diamine monomers used in conventional solution polymerization. In addition, their thermal and optical properties were also investigated. All polymers showed high thermostabilities (Tg ∼ 320 °C, Td5 (N2) ∼ 466 °C, residue at 800 °C under nitrogen ∼69.0%) and adequate solubilities in polar organic solvents. Films prepared by the solvent-cast method showed good transparencies, which mainly depended on the diamine structure as opposed to the dichloride moiety. The refractive indices at the D-line (589 nm) of the PG films were unexpectedly high, between 1.677 and 1.800, compared to those of common organic optical polymeric resins. The incorporated melamine moieties afforded effective dense packing with the polycyclic aromatic hydrocarbon groups filling the free spaces between rigid polymer chains, resulting in unusually high refractive indices. The PG polymer solution in N-methylpyrrolidone showed strong blue fluorescence (371–471 nm) with a quantum yield of up to 98%.

Reduction of the cationic growing center of polyisobutylene by activated magnesium. Block copolymerization of isobutylene with tert-butyl methacrylate

Transformation of the tert-chlorine end group of poly(isobutylene) into a terminal Grignard group was studied with the motivation of producing a PIB macroanion. The reduction of the terminal tert-chlorine group was completed within 30 min at room temperature by using activated magnesium (Mg * ) prepared by the reaction of MgCl 2 with lithium naphthalenide. The efficiency of the transformation was 28%, which was determined by end-group analysis of the polymer obtained after quenching the reduction with methyl 2-phenylacetate in the presence of CeCl 3 . The terminal carbanion prepared by this method initiated the polymerization of tert-butyl methacrylate (TBMA) to give a block copolymer consisting of an anionically and a cationically polymerizable monomer.