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研究生: Nattinee Krathumkhet
Nattinee Krathumkhet
論文名稱: Bio-based materials in biomedical applications
Bio-based materials in biomedical applications
指導教授: 今榮東洋子
Toyoko Imae
氏原真樹
Masaki Ujihara
口試委員: 呉乃立
Nae-Lih Wu
袁俊傑
Chiun-Jye Yuan
王復民
Fu-Ming Wang
氏原真樹
Masaki Ujihara
今榮東洋子
Toyoko Imae
學位類別: 博士
Doctor
系所名稱: 應用科技學院 - 應用科技研究所
Graduate Institute of Applied Science and Technology
論文出版年: 2021
畢業學年度: 109
語文別: 英文
論文頁數: 117
中文關鍵詞: nitric oxide gashierarchical nanocompositecarbon nanohornpoly(amido amine) dendrimerfluorinated poly(ethylene glycol)pectinbacterial cellulosepolypyrroleibuprofen
外文關鍵詞: nitric oxide gas, hierarchical nanocomposite, carbon nanohorn, poly(amido amine) dendrimer, fluorinated poly(ethylene glycol), pectin, bacterial cellulose, polypyrrole, ibuprofen
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本文內容主要討論生物基材在生物醫學中的應用, 即由碳基材料組成的治療性氣體, 奈米載體中保留一氧化氮 (NO), 以及薄膜狀果膠/細菌纖維素複合材料的電控貼片, 用於藥品的傳遞。在研究碳基材料的保存性方面, 一氧化氮作為治療氣體通過碳基材料的製備而被裝載到奈米載體中,即奈米碳角材料 (CNH), 通過樹枝狀聚合物的分級組裝而製成聚 (酰胺基胺), 具有碳氟化合物結合 (DEN-F) 和氟化聚乙二醇 (F-PEG). 這些奈米載體材料中 NO氣體的負載和保留能力隨 CNH 中的氮摻雜以及 DEN-F 和 F-PEG 的分層形成而增加. 然後, 保存的 NO 氣體達到了 312±50µmol/mg 的流量. 此外, 針對細菌 (大腸桿菌和金黃色葡萄球菌) 的抗菌作用取決於所保存的 NO 氣體量而增加. 因此, CNH 中的球型同心層結構優先用於,分層結構的空隙中緩慢釋放 NO 氣體. NO 氣體的這種持續釋放有利於使用在生物醫學氣體療法, 針對細菌和其他寄生蟲的治療. 關於果膠 / 細菌纖維素複合材料的電控貼片 , 是將果膠中的水凝膠添加到細菌纖維素(BC) 和導電聚合物(聚吡咯, Ppy)中, 製成薄膜基質. Ppy已成功地摻入並嵌入到果膠/ BC 水凝膠複合物中,作為藥物封裝主體,在所施加的電場下具有出色的物理化學和生物學特性.布洛芬(Ibuprofen) 是一種非類固醇消炎藥 (NSAID), 用來止痛, 退燒和消炎. 布洛芬水凝膠複合材料在改良的 Franz 擴散池, pH 5.5 和 7.4 緩衝溶液中進行釋放 15 小時. 結果證明,隨著 BC 含量和施加電壓的增加, 藥物可以持續增加釋放. 在 7 V 的電壓時, 布洛芬在 Ppy/果膠/BC 上有最佳釋放率 78%. 此外, 這種水凝膠複合材料提供了一種可能的替代基質材料, 尤其是對革蘭氏陽性細菌發揮了抗菌作用. 這些結果不僅有助於無痛電穿孔促進藥物之經皮吸收研究, 而且也助於生物醫學研究領域.


In this dissertation, I mainly discuss about bio-based materials toward biomedical applications namely conservation of nitric oxide (NO) in therapeutic gas nanocarrier consisting of carbon-based materials and electrically controlled transdermal patch of film pectin/bacterial cellulose composites for drug delivery. On the research of conservation of carbon-based materials, nitric oxide as a therapeutic gas were loaded into nanocarrier materials via a fabrication of carbon based materials, namely, carbon nanohorn -based materials (CNH) through hierarchical assembly of poly(amido amine) dendrimer with fluorocarbon binding sites (DEN-F) and fluorinated poly(ethylene glycol) (F-PEG). The loading and conservation abilities of NO gas in these nanocarrier materials increased with the nitrogen doping in CNH and hierarchy formation by DEN-F and F-PEG. Then, the conserved NO gas reached up to 312±50 µmol/mg carrier. Moreover, the antimicrobial effects on bacteria (E. coli and S. aureus) increased depending on the conserved amount of NO gas. Thus, the concentric hierarchy on spherical CNH is preferable for slow release of NO gas from the void volume in hierarchies. This sustained release of NO gas is advantageous to the potential biomedical gas therapy against bacteria and other parasites. Regarding the electrically controlled transdermal patch film of pectin/bacterial cellulose composites, the hydrogel of pectin was added to bacteria cellulose (BC) and conductive polymer (polypyrrole, Ppy) and fabricated as a film matrix. Ppy was successfully incorporated and embedded into the pectin/BC hydrogel composites as the drug encapsulation host under the applied electrical field which offers the excellent physicochemical and biological properties. Ibuprofen is a narcotic analgesic for symptomatic treatment. The drug release of ibuprofen from the hydrogel composite matrix for 15 h was performed in buffer solutions of pH 5.5 and 7.4 with modified Franz diffusion cell. The results showed that the sustainable release of drug increased with increasing the BC content and the applied electrical potential. The optimum ibuprofen release of 78% on Ppy/pectin/BC was achieved under applied electrical potential at 7 V. In addition, this hydrogel composites presented one of the possible alternative matrix materials exerting antibacterial activity especially for gram-positive bacteria. These results contribute not only to transdermal iontophoresis drug delivery research but also to biomedical research areas.

TABLE OF CONTENTS PAGE Title Page i Abstract (in English) iv Abstract (in Chinese) v Acknowledgements vi Table of Contents viii List of Tables xi List of Figures xii CHAPTER I GENERAL BACKGROUND 1 II Nitric oxide gas conservation in carbon nanohorn/fluorinated dendrimer/fluorinated PEG-based hierarchical composites as therapeutic nanocarriers 1. Theoretical background and literature reviews 3 1.1. Theraputic gases 3 1.2. Nitric oxide (NO) 4 1.3. Nanomedicine materials carrier 4 1.4. Motivation and objective 12 2. Experimental section 13 2.1. Materials and reagents 13 2.2. Preparation of graphene oxide (GO) by a modified Hummers method 13 2.3. Preparation of carbon nanohorns oxide acid-treated (CNHacid) 14 2.4. Preparation of the N-doped reduced graphene oxide (NG) or N-doped CNH acid-treated (NCNH) 14 2.5. Preparation of the NG and NCNH mixed with DEN-F 15 CHAPTER PAGE 2.6. Preparation of the NG or NCNH /DEN-F coated F-PEG 16 2.7. Determination of NO gas by griess assay method 17 2.8. Characterizations 19 3. Results and discussion 21 3.1. Conservation ability of NO gas on gas carrier nanomaterials 21 3.2. Characterization of carrier nanomaterials 26 3.3. Assessment of the antimicrobial activity of the nanomaterials 36 3.4. NO gas conservation in hierarchical nanocomposites 38 4. Conclusion 41 III Film-type pectin-bacterial cellulose/polypyrrole hydrogel composites for electrically controlled transdermal drug delivery 1. Theoretical background and literature reviews 42 1.1. Drug delivery systems (DDS) 42 1.2. Skin structure 43 1.3. Hydrogel 44 1.4. Pectin 45 1.5. Bacterial cellulose 46 1.6. Conductive polymer 47 1.7. Motivation and objective 51 2. Experimental section 51 2.1. Materials and reagents 51 2.2. Preparation of pectin hydrogel 51 2.3. Preparation of bacterial cellulose hydrogel 52 2.4. Preparation of ibuprofen-loaded Pectin/Bacterial cellulose hydrogel composite 52 2.5. Preparation of ibuprofen doped- polypyrrole 52 2.6. Preparation of ibuprofen doped- polypyrrole Pectin/Bacterial cellulose hybrid hydrogel composites 53 CHAPTER PAGE 2.7. Characterizations 53 3. Results and discussion 58 3.1. Characterization pectin/BC hydrogel composites 58 3.2. Drug-release from ibuprofen-loaded pectin/BC hydrogel composite 63 3.3. Release of-ibuprofen from Ppy pectin/BC 30 wt% hydrogel composites 67 3.4. Antibacterial activity 70 4. Conclusion 73 IV GENERAL CONCLUSIONS AND FUTURE PERSPECTIVES 74 REFERENCES 76 CURRICULUM VITAE 91 APPENDIX Document publication of qualification on research work for Master to Ph.D. Fast-track program 93

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