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  1. 学位論文
  2. 学位論文

生分解性有機-無機複合球状粒子の創製とその生物学的性質に関する研究

https://doi.org/10.18997/00006894
https://doi.org/10.18997/00006894
9f7073f0-27f5-494f-94e3-49e877490243
名前 / ファイル ライセンス アクション
sei_k_312.pdf sei_k_312.pdf (7.7 MB)
アイテムタイプ 学位論文 = Thesis or Dissertation(1)
公開日 2018-08-31
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
タイトル
タイトル Preparation and biological properties of biodegradable organic-inorganic hybrid spheres
言語 en
タイトル
タイトル 生分解性有機-無機複合球状粒子の創製とその生物学的性質に関する研究
言語 ja
言語
言語 eng
著者 Da Cruz Neves, Susana

× Da Cruz Neves, Susana

en Da Cruz Neves, Susana

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内容記述タイプ Abstract
内容記述 Antibiotic resistance in bacteria is a serious problem that requires researchers to engineer new strategies to tackle this growing threat. The limited intracellular bioavailability of antibiotics decreases the efficacy of the treatments and, as a consequence promotes bacterial resistance towards antibiotics. Therefore, the development and improvement of drug controlled release systems is vital to create new approaches to deliver in the most effective manner the drugs or other bioactive compounds to the desired location. Especially if the targeted site is the gastrointestinal track, where the environmental conditions are harsh for biomolecules to maintain its stability and function. Polymeric microspheres are attractive due to their biodegradability and ability to encapsulate drugs or bioactive agents, therefore increasing their bioavailability. To address these poor bioavailability or unsustained drug release challenges, chitosan microspheres are adequate as drug delivery carriers for the gastrointestinal track due to mucoadhesive properties, which allows the drug dosage to be retained in the gastrointestinal track for extended periods of time, in addition to the presence of reactive sites in chitosan which allow the interaction with biomolecules to be carried to the targeted site. Spherical particles were produced using chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS) as an organic-inorganic hybrid compound resorting to two different methods. The first method consisted in a microfluidic approach using chitosan–GPTMS–β-glycerophosphate (chitosan–GPTMS–β-GP) to produce microspheres with uniform size and spherical shape around 650 μm and 285 μm. Whereas, in the second method beads with diameter around 2 mm with micropores were synthetized by dropping the hybrid precursor sol into liquid nitrogen followed by a freeze drying process. The physicochemical characterization of the microspheres from the microfluidic system was performed in which the formation of siloxane (Si-O-Si) networks was confirmed in the chitosan polymeric matrix, as well as the spheres stability in solutions. The degradation of microspheres with different GPTMS molar ratios was evaluated under simulated gastric fluids (SGF) and neutral conditions. The microspheres incubated at pH 7.4 had the lowest weight loss (27%–32%), whereas those incubated at pH 1.7 and pH 5.4 showed greater weight losses of 43–59% and 69–77%, respectively. The inhibition of the degradation at low pH was dependent on the siloxane network formed in the chitosan matrix. Additionally, GPTMS was released with the chitosan chains via hydrolysis of the chitosan molecules. Pelargonidin is a natural antioxidant which was incorporated in the microspheres and the releasing behavior was observed under SGF conditions and simulated time of digestion cycle in humans. The release profile observed leads to believe that these microspheres are promising for gastrointestinal drug delivery applications due to its resistance to low pH conditions present in the upper gastrointestinal track, in addition to the controlled and sustained release rate of pelargonidin and its ability to retain it in the matrix even after 57 h. Cerium compounds have been described to possess antibacterial activity, and new strategies of treating pathogenic bacteria are needed due to the rapid increase of bacterial resistance towards common antibiotics. The bacterial behavior of Escherichia coli and Staphylococcus aureus was observed with the chitosan–GPTMS–β-GP spheres and hydrogels containing cerium(III) chloride (CeCl3), and no antibacterial effect was observed due to the immediate interaction between β-GP and cerium, via the complex formation of cerium with the amino groups of chitosan, making it inaccessible to the bacteria. Furthermore, the bacterial viability increased for both gram-negative and gram-positive strains on hydrogels with and without cerium. To achieve antibacterial applications using the chitosan-siloxane hybrid, beads without β-GP were prepared by dropping the chitosan-GPTMS precursor sols into liquid nitrogen. The beads were synthetized with and without cerium. The bacterial activity was greatly reduced with the highest tested amounts of cerium against both gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) strains. This microporous beads have the potential to be applied for soft tissue defect fillers materials with antibacterial properties to reduce or eradicate in situ bacterial infection.
言語 en
目次
内容記述タイプ TableOfContents
内容記述 1. General Introduction||2. Synthesis of Chitosan-Siloxane Hybrid Microspheres Using A Microfluidic Approach and Release of Pelargonidin In Gastrointestinal Simulated Conditions||3. Bacterial Behavior on Chitosan-Siloxane Hybrid Microspheres and Hydrogels Containing Cerium||4. Bacterial Behavior with Chitosan-Siloxane Hybrid Spherical Beads Containing Cerium
備考
内容記述タイプ Other
内容記述 九州工業大学博士学位論文 学位記番号:生工博甲第312号 学位授与年月日:平成30年3月23日
キーワード
主題Scheme Other
主題 Inorganic-organic hybrid
キーワード
主題Scheme Other
主題 Porous Spheres
キーワード
主題Scheme Other
主題 Biodegradable polymer
キーワード
主題Scheme Other
主題 Drug Delivery
キーワード
主題Scheme Other
主題 Bacteria
アドバイザー
宮崎, 敏樹
学位授与番号
学位授与番号 甲第312号
学位名
学位名 博士(工学)
学位授与年月日
学位授与年月日 2018-03-23
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 17104
学位授与機関名 九州工業大学
学位授与年度
内容記述タイプ Other
内容記述 平成29年度
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
ID登録
ID登録 10.18997/00006894
ID登録タイプ JaLC
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