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工学教育研究部 工学科応用物質化学プログラム担当 |
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Khan N.F., Nakamura H., Izawa H., Ifuku S., Kadowaki D., Otagiri M., Anraku M.
Journal of Functional Biomaterials 14 ( 7 ) 2023年7月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Functional Biomaterials
Arginine-rich membrane-permeable peptides (APPs) can be delivered to cells by forming complexes with various membrane-impermeable bioactive molecules such as proteins. We recently reported on the preparation of guanidinylated chitosan (GCS) that mimics arginine peptides, using chitosan, a naturally occurring cationic polysaccharide, and confirmed that it enhances protein permeability in an in vitro cell system. However, studies on the in vivo safety of GCS are not available. To address this, we evaluated the in vivo safety of GCS and its translocation into the gastrointestinal tract in rats after a single oral administration of an excessive dose (500 mg/kg) and observed changes in body weight, major organ weights, and organ tissue sections for periods of up to 2 weeks. The results indicated that GCS causes no deleterious effects. The results of an oral administration of rhodamine-labeled chitosan and an evaluation of its migration in the gastrointestinal tract suggested that the disappearance of rhodamine-labeled GCS from the body appeared to be slower than that of the non-dose group and pre-guanidinylated chitosan due to its mucoadhesive properties. In the future, we plan to investigate the use of GCS to improve absorption using Class III and IV drugs, which are poorly water-soluble as well as poorly membrane-permeable.
DOI： 10.3390/jfb14070340
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Water-soluble guanidinylated chitosan: a candidate material for protein delivery systems 査読あり
Izawa H., Yagi A., Umemoto R., Ifuku S.
Polymer Journal 55 ( 8 ) 885 - 895 2023年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Polymer Journal
Here, we introduce water-soluble guanidinylated chitosan (WGCS) as a candidate material for protein delivery systems to enhance the cellular internalization of protein/peptide drugs. A WGCS composed of 48.2% guanidinylated chitosan, 20.6% chitosan, and 31.2% chitin units was prepared with a low-molecular-weight chitosan (CS) lactate via a guanidinylation reaction with 1-amidinopyrazole hydrochloride. The Mn of WGCS was estimated by gel permeation chromatography analysis to be 7.6 × 103 (Mw /Mn = 1.5). The higher chitin content in WGCS than in common CS (<20%) is an important factor in achieving water solubility. WGCS showed ca. 2.5-fold higher internalization into HeLa cells than CS does. This clearly indicated that guanidinylation enhances internalization. In addition, endocytic pathways were suggested as a mechanism underlying internalization. Moreover, WGCS significantly enhanced the internalization of bovine serum albumin (BSA) in transport medium at pH 7.4 containing BSA: the internalized amount of BSA in the presence of WGCS was ca. 2-fold higher than in the presence of CS. This higher internalization was caused by efficient binding between WGCS and BSA via electrostatic interactions owing to the guanidino groups. Indeed, the affinity of the binding sites of WGCS is more than 10-fold higher than that of the binding sites of CS.
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Preparation of Nanochitin from Crickets and Comparison with That from Crab Shells 査読あり
Kishida K., Mizuta T., Izawa H., Ifuku S.
Journal of Composites Science 6 ( 10 ) 2022年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Composites Science
Crickets are gaining worldwide attention as a nutrient source with a low environmental impact. We considered crickets as a new source of chitin raw material. Chitin isolated from crickets was successfully converted to nanochitin by pulverization. First, chitin was obtained from cricket powder in a 2.6% yield through a series of chemical treatments. Chitin identification was confirmed by FT-IR and 13C NMR. The chitin had an α-type crystal structure and a deacetylation degree of 12%. Next, it was pulverized in a disk mill to obtain nanochitin. Cricket nanochitin was of a whisker shape, with an average fiber width of 10.1 nm. It was larger than that of crab shells, while the hydrodynamic diameter and crystal size were smaller. Such differences in shape affected the physical properties of the dispersion. The transmittance was higher than that of crab nanochitin due to the size effect, and the viscosity was smaller. Moreover, the dry non-woven cricket nanochitin sheets were more densely packed, and their modulus and breaking strength were greater.
DOI： 10.3390/jcs6100280
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Izawa H., Ishisaka S., Saimoto H., Ifuku S.
Bulletin of the Chemical Society of Japan 95 ( 9 ) 1289 - 1295 2022年9月
担当区分：筆頭著者, 責任著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Bulletin of the Chemical Society of Japan
The effects of the physical properties of skin layers and substrates on drying-induced surface wrinkling are investigated with a system using chitosan films having polyion complex (PIC) skin layers. The PIC layers are fabricated with diverse anionic polymers having similar molecular weights on a chitosan (CS) film surface, and the films are dried. In all cases, surface wrinkles form but their sizes vary widely depending on the molecular structure. In particular, wrinkles formed with ligninsulfonate are much larger than those formed with the others. The skin layers differ significantly in surface hardness but not in thickness, indicating that wrinkle sizes induced by PIC skin layers are predominately determined by the hardness of the layers or by physical properties affected by hardness, such as shrinkage volume. The effects of the elastic moduli and shrinkage volume of the substrates are evaluated with higher molecular weight CS and surface-deacetylated chitin nanofiber composite CS films that have different elastic moduli but show very similar swellingdrying behaviors. The wrinkle sizes and skin layer thicknesses also suggest that wrinkle size in this system depends on the hardness of the skin layers or on the physical properties affecting the hardness.
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Optimization of Chitin Nanofiber Preparation by Ball Milling as Filler for Composite Resin 査読あり
Zewude D.A., Izawa H., Ifuku S.
Journal of Composites Science 6 ( 7 ) 2022年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Composites Science
Chitin nanofiber is a nanomaterial produced by pulverizing chitin, the main component of crab shells. Since it has excellent mechanical properties, it is expected to be used as a reinforcing material to strengthen materials. Chitin was mechanically ground in water using a ball mill to prepare nanofibers. The ball size, total ball weight, and milling time were varied, and the resulting water dispersion and the cast film were analyzed to optimize the conditions for efficient preparation. The length and width of the nanofibers were also measured by SEM and AFM observations. The size of the balls affected the level of grinding and the intensity of impact energy on the chitin. The most efficient crushing was achieved when the diameter was 1 mm. The total ball weight directly affects the milling frequency, and milling proceeds as the total weight increases. However, if too many balls occupy the container, the grinding efficiency decreases. Therefore, a total ball weight of 300 g was optimal. Regarding the milling time, the chitin becomes finer depending on the increase of that time. However, after a specific time, the shape did not change much. Therefore, a milling time of approximately 150 min was appropriate.
DOI： 10.3390/jcs6070197
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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微細構造表面を誘起するスキン層の科学の開拓
研究課題/領域番号：19K05616 2019年04月 - 2022年03月
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
井澤 浩則
担当区分：研究代表者
その他競争的資金獲得実績 【 表示 ／ 非表示 】
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グアニジル化キトサンライブラリの構築
2024年08月 - 2026年03月
国立研究開発法人新エネルギー・産業技術総合開発機構 （NEDO） 官民による若手研究者発掘支援事業／マッチングサポートフェーズ（NEDO）
担当区分：研究代表者