Katsuhiko Nakamae

Biomolecule-sensitive hydrogels

Stimuli-sensitive hydrogels have attracted considerable attention as intelligent materials in the biochemical and biomedical fields, since they can sense environmental changes and induce structural changes by themselves. In particular, biomolecule-sensitive hydrogels that undergo swelling changes in response to specific biomolecules have become increasingly important because of their potential applications in the development of biomaterials and drug delivery systems. This article provides an overview of the important and historical research regarding the synthesis and applications of glucose-sensitive hydrogels which exhibit swelling changes in response to glucose concentration. Enzymatically degradable hydrogels and antigen-sensitive hydrogels are also described in detail as protein-sensitive hydrogels that can respond to larger biomolecules. The synthetic strategies of other biomolecule-sensitive hydrogels are summarized on the basis of molecular imprinting and specific interaction. The biomolecule-sensitive hydrogels reviewed in this paper are expected to contribute significantly to the exploration and development of newer generations of intelligent biomaterials and self-regulated drug delivery systems.

Kenaf reinforced biodegradable composite

Abstract Mechanical properties of environmentally friendly composite made of kenaf fibre and poly- l -lactic acid (PLLA) resin was investigated. Youngs modulus (6.3 GPa) and the tensile strength (62 MPa) of the kenaf/PLLA composite (fibre content=70 vol.%) were comparable to those of traditional composites. These properties were higher than those of the kenaf sheet and the PLLA film themselves. This is considered to attribute to the strong interaction between the kenaf fibre and PLLA. In addition, the storage modulus of the composite remain unchanged up to the melting point of PLLA. The effects of the molecular weight of PLLA, the orientation of the kenaf fibres in the sheet on the mechanical properties of the composite were also investigated. It was found that kenaf fibre can be a good candidate for the reinforcement fibre of high performance biodegradable polymer composites.

An AB block copolymer of oligo(methyl methacrylate) and poly(acrylic acid) for micellar delivery of hydrophobic drugs

An AB block copolymer of oligo(methyl methacrylate) (oMMA) and poly(acrylic acid) (PAAc) has been synthesized. The block copolymer forms micelles in an aqueous medium, as confirmed by a fluorescence probe technique using pyrene. Doxorubicin hydrochloride was incorporated into the micelle and the release profile of doxorubicin hydrochloride was investigated. Slow and prolonged release of doxorubicin hydrochloride from the micelle was observed. The AB block copolymer micelle can be useful for prolonged mucosal drug delivery of hydrophobic drugs.

Really smart bioconjugates of smart polymers and receptor proteins

Over the past 18 years we have been deeply involved with the synthesis and applications of stimuli-responsive polymer systems, especially polymer-biomolecule conjugates. This article summarizes our work with one of these conjugate systems, specifically polymer-protein conjugates. We include conjugates prepared by random polymer conjugation to lysine amino groups, and also those prepared by site-specific conjugation of the polymer to specific amino acid sites that are genetically engineered into the known amino acid sequence of the protein. We describe the preparation and properties of thermally sensitive random conjugates to enzymes and several affinity recognition proteins. We have also prepared site-specific conjugates to streptavidin with temperature-sensitive polymers, pH-sensitive polymers, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed in this article.

Elastic modulus of the crystalline regions of chitin and chitosan

The elastic moduli El of the crystalline regions of α-chitin and chitosan in the direction parallel to the chain axis were measured by X-ray diffraction. The El values were 41 GPa for α-chitin, and 65 GPa for chitosan, respectively, at 20°C. The contracted skeletons of α-chitin and chitosan are the key factor for the low El values compared with that (138 GPa) of cellulose I. The El value of α-chitin was constant at 41 GPa both at −190°C and 150°C, which indicates that the molecular chain of α-chitin is stable against heat within the temperature and stress range studied.

Preparation of reversibly glucose-responsive hydrogels by covalent immobilization of lectin in polymer networks having pendant glucose

Glucose-responsive hydrogels were prepared by copolymerization of a monomer having a pendant glucose with modified lectin (concanavalin A (ConA)) having vinyl groups. Swelling behavior of ConA-copolymerized glucosyloxyethyl methacrylate (GEMA) hydrogels was discussed from the viewpoint of their synthetic condition and structures. The swelling ratio of the ConAcopolymerized GEMA hydrogels was strongly dependent on the glucose concentration in a buffer solution. As free glucose resulted in the dissociation of the complex between ConA and pendant glucose in the networks and the cross-linking density in the hydrogel decreased, the hydrogels swelled gradually in the presence of free glucose. Leak of ConA from the ConA-entrapment hydrogel and ConA-copolymerized hydrogel was examined in order to discuss the reversible changes of their glucose-responsive behavior. During swelling in the presence of free glucose, ConA leaked out of the ConA-entrapment GEMA hydrogel but did not out of the ConA-copolymerized GEMA hydrogel. As a result, the ConA-copolymerized GEMA hydrogel showed the reversible swelling changes in response to a stepwise change in the glucose concentration. This study revealed that covalent immobilization of ConA in the GEMA networks is very important for development of reversibly glucose-responsive hydrogels.

A hydrophobically-modified bioadhesive polyelectrolyte hydrogel for drug delivery

A hydrophobically-modified bioadhesive polyelectrolyte hydrogel has been prepared by grafting oligomers of methyl methacrylate (MMA) to the backbone of a poly(acrylic acid) (PAAc) hydrogel. Swelling behaviour and drug release profiles of the hydrogel have been studied for six model drugs. The higher the graft level of the oMMA, the slower the swelling as well as the lower the extent of swelling, probably due to the higher concentration of hydrophobic grafts and their aggregation into domains within the hydrogel. The drug release profile from the hydrogels was investigated using phosphate buffered saline (PBS) as a release medium. In the case of hydrophilic drugs, such as theophylline, the drug release rate was enhanced by the oMMA modification. The formation of hydrophobic domains might enlarge the aqueous pore sizes of the hydrogel, thus permitting the hydrophilic drug to diffuse out more rapidly. On the contrary, for moderately hydrophobic drugs such as propranolol hydrochloride, the release rate was slowed down by the oMMA modification. This is probably due to favoured absorption of the hydrophobic groups of the drug into the oMMA domains and the lack of interconnections between the domains. Our results also suggest that ionic interaction of the cationic drug, propranolol hydrochloride, with the network is fairly weak and that hydrophobic interactions seem to be the major force for loading propranolol hydrochloride in the hydrogel. In the case of a positively charged protein, such as lysozyme, the higher the graft level of the OMMA, the slower the release. In addition to its ionic interaction with the PAAc, lysozyme seems also to interact with the hydrophobic domains which can slow or even limit its ionic exchange-driven release mechanism. The hydrophobically-modified bioadhesive hydrogel could be useful for sustained release of hydrophobic drugs or oppositely-charged proteins.

Refilling the lens with an inflatable endocapsular balloon: surgical procedure in animal eyes

In this report we describe the surgical details involved in refilling the lenses of 13 rabbit and 3 primate eyes using an inflatable endocapsular balloon to restore accommodation. The procedure involves endocapsular phacoemulsification through a small “buttonhole” or “dumbbell” anterior capsulotomy or minicircular capsulotomy and the simultaneous preservation of capsular integrity, including the zonules and ciliary muscles. An inflatable balloon made of thin silicone membrane is then inserted into the empty capsular bag. A liquid silicone polymer is injected into the balloon through a delivery tube, and the empty capsular bag is refilled by the inflated balloon. The procedure was found to be reproducible, and an accommodation of 6 D was confirmed in one primate eye. Capsular opacification occurred, but the proliferation and migration of residual lens epithelial cells could be hindered by abundant refilling. This lens-refilling technique may provide restoration of accommodation in future cataract surgery.

Formation of poly(glucosyloxyethyl methacrylate)-Concanavalin A complex and its glucose-sensitivity

The complex formation between Concanavalin A (Con A) and a polymer having pendant glucose groups was studied in order to design a glucose-sensitive polymer. The polymer having pendant glucose (poly(glucosyloxyethyl methacrylate) or (poly(GEMA)) forms a complex with Con A in tris HCl buffer (pH = 7.5). The solution then becomes turbid due to the multiple associations between poly(GEMA) and Con A. When free glucose or mannose are added to the turbid solution, the solution becomes transparent again. However, the addition of galactose does not cause the solution to be transparent. This indicates that Con A prefers to form a complex with free glucose or mannose (but not galactose) rather than with the pendant glucose in poly(GEMA). Therefore, the complex between poly(GEMA) and Con A is expected to be glucose- and mannose-sensitive. The apparent dissociation constants of the complexes between saccharide (poly(GEMA), glucose, and mannose) and Con A were also determined by affinity electrophoresis.

Optical and atomic force microscopy of an explanted AcrySof intraocular lens with glistenings

Purpose: To assess the surface morphology and cause of glistenings in an explanted AcrySof® intraocular lens (IOL). Setting: Shakai Hoken Kobe Central Hospital, Kobe, Japan. Methods: A 63‐year‐old Japanese man had implantation of an AcrySof IOL in the capsular bag. One month postoperatively, he had a neodymium:YAG laser capsulotomy for posterior capsule opacification, which changed the IOLs position in the capsular bag. A few months later, the patient developed disabling night glare from intralenticular glistenings and progressive hyperopic refractive error. The IOL was explanted and then analyzed by optical microscopy and atomic force microscopy (AFM). Laboratory analysis of control AcrySof IOLs kept in a balanced salt solution at steady room and body temperature for 2 months was also performed to evaluate the cause of the glistenings observed clinically. Results: Optical microscopy showed that the explanted AcrySof IOL had several microvacuoles; no abnormalities were observed in the control AcrySof IOLs before or after folding at the room and body temperatures. The AFM analysis showed a significant change in the surface morphology of the explanted IOL, including vacuolar formations in the posterior surface as well as numerous anterior surface irregularities. No microvacuoles or surface morphology alterations were observed in the control AcrySof IOLs by AFM analysis. Conclusion: The glistenings in the explanted AcrySof IOL were likely caused by temperature changes and not mechanical stress from folding.