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研究生： 艾玉寧
Aning Ayucitra
論文名稱： 氧化石墨烯-羧甲基纖維素複合材料之合成及定性以作為對酸鹼值靈敏阿黴素之控制釋放
Synthesis and characterization of graphene oxide-carboxymethyl cellulose composite materials for pH-sensitive, controlled release of doxorubicin
指導教授： 朱義旭
Yi-Hsu Ju
口試委員: Suryadi Ismadji
Suryadi Ismadji
Truong Chi Thanh
Truong Chi Thanh
Huynh Lien Huong
Huynh Lien Huong
Tran Nguyen Phuong Lan
Tran Nguyen Phuong Lan
Artik Elisa Angkawijaya
Artik Elisa Angkawijaya
Alchris Woo Go
Alchris Woo Go
朱義旭
Yi-Hsu Ju
學位類別： 博士
Doctor
系所名稱： 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年： 2020
畢業學年度： 108
語文別： 英文
論文頁數： 84
中文關鍵詞： 羧甲基纖維素 、複合膜 、阿黴素 、藥物載體 、氧化石墨烯 、水凝膠珠
外文關鍵詞： Carboxymethyl cellulose, Composite films, Doxorubicin, Drug carrier, Graphene oxide, Hydrogel beads
相關次數： 點閱：380  下載：3 
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    • 氧化石墨烯(GO)為基礎之奈米材料因具有獨特結構及特性使其在生醫上有諸多應用，特別是在生物感測器、標靶藥物傳送、人造組織及生物啟發材料。結合GO及生物聚合物或可改善其溶解度及生物相容性以及其他功能，例如對溫度及 酸鹼度支應答。
    本研究之目的著重於合成應用在藥物輸送之以GO為基礎之複合材料、定性及應用潛力。利用物理性交聯羧甲基纖維素與分散相GO合成具選擇性藥劑釋放性質之複合水膠珠及膜以作為對酸鹼靈敏之藥劑載體。GO則是以無觸媒、溫和反應溫度、修正之Hummers’法合成。使用X射線粉末衍射、FT-IR光譜儀、拉曼光譜儀、TGA及FE-SEM 顯微鏡對GO及GO/CMC複合材料定性，除確定成功合成GO及GO/CMC複合材料外，並了解GO及 GO/CMC複合材料之性質與其作為藥劑載體表現之關聯。以阿黴素(DOX) 當作模型藥物，本研究也探討合成GO時之溫度及在製作珠粒時GO 分散濃度對DOX負載能力及DOX釋放之影響。
    由所得 ID/IG = 0.991及 C/O 比= 1.94顯示在50 oC可合成具有不錯氧化程度之GO (GO-50)。環境之酸鹼度對GO/CMC複合材料之膨潤性質有重大影響。正比於膨潤性質，水膠珠中所含之GO使其有較高之DOX負載能力。從GO-50在使用分散濃度為5 mg/mL所得水膠珠粒 (GCB-50.5) 及水膠複合膜 (GCF-50.5) 對DOX負載能力分別為 4.2494 mg/g及19.5977 mg/g，顯示有許多含氧之官能基。DOX從該兩種載體之釋放行為顯示二者均對酸鹼度敏感。
    利用MTT試驗對7F2做體外細胞毒性測試，結果顯示兩種複合材料都比其GO前驅物有較佳之細胞存活率。是以本研究所製作得複合材料有潛力使用作有效、可行的DOX載體。

    Graphene oxide (GO)-based nanomaterials possess unique structures and behaviors leading to their wide biomedical applications especially in biosensors, targeted drug delivery systems, artificial tissues, and bioinspired materials. Combining GO with biopolymers may improve its solubility and biocompatibility, and other functionalities such as temperature- and pH-response.
    This study focused on the synthesis, characterizations, and potential application of GO-based composite materials in drug delivery. Composite hydrogels beads and films were synthesized by physically cross-linked carboxymethyl cellulose (CMC) with GO dispersion to produce a pH-sensitive drug carrier with selective drug-release properties. GO was prepared according to a catalyst-free modified Hummers’ method at mild oxidation temperatures. Characterizations using X-ray powder diffraction, FT-IR spectroscopy, Raman spectroscopy, TGA, and FE-SEM microscopy were performed not only to confirm the successful synthesis of GO and GO/CMC composites but also to fully understand the relationship between GO’s properties and the derived composite materials’ properties and their performance as drug carrier. With doxorubicin (DOX) as the model drug, the effects of oxidation temperature during GO preparation and concentration of GO dispersion used in the prepared beads on DOX-loading capacity and its releasing profiles were also studied.
    A mild oxidation temperature of 50 oC could produce GO (GO-50) with satisfactory oxidation degree as shown by ID/IG and C/O ratios of 0.991 and 1.94, respectively. It was observed that swelling behavior of GO/CMC composite materials depended significantly on pH of environment. Proportionally to the swelling behavior, the presence of GO within hydrogels resulted in higher DOX loading capacity of the prepared beads. The highest DOX-loading capacity was 4.2494 mg/g and 19.5977 mg/g for GO/CMC hydrogel beads (GCB-50.5) and composite films (GCF-50.5), respectively, which were synthesized from GO-50 with a dispersion concentration of 5 mg/mL, corresponding to its abundant oxygen-containing functional groups. The release profile of DOX from both composites also indicated a strong pH-sensitive behavior.
    The in vitro cytotoxicity tests on 7F2 cells by MTT assay revealed that both composite materials have a higher percentage of viability than that of their GO precursors. The prepared composites thus can potentially be used as an effective and viable DOX carrier.

    COVER i RECOMMENDATION LETTER ii QUALIFICATION LETTER iii ABSTRACT IN CHINESE iv ABSTRACT IN ENGLISH v ACKNOWLEDGEMENT vi TABLE OF CONTENTS viii LIST OF ABBREVIATIONS xi LIST OF TABLES xiii LIST OF FIGURES xiv CHAPTER 1 INTRODUCTION 1 1.1 Background 1 1.2 Research objectives 5 CHAPTER 2 LITERATURE REVIEW 7 2.1 Graphene oxide 7 2.2 GO-based nanocomposite materials and the use in drug delivery studies 13 2.2.1 Functionalization of GO with biopolymers 13 2.2.2 GO/CMC composite materials 14 2.3 Various drugs applied in drug delivery studies 16 2.3.1 Doxorubicin 17 2.3.2 Loading and release studies of doxorubicin 18 2.4 Cytotoxicity studies 20 2.5 Essential characterizations 22 2.5.1 X-Ray Powder Diffraction (XRD) 22 2.5.2 Raman Spectroscopy 22 2.5.3 Fourier Transform Infrared Spectroscopy (FT-IR) 23 2.5.4 Field Emission Scanning Electron Microscopy with Energy Dispersive X-Ray Spectroscopy (FESEM-EDX) 23 CHAPTER 3 MATERIALS AND METHODS 24 3.1 Materials 25 3.2 Equipments 26 3.3 Preparation of graphene oxide 27 3.4 Preparation of GO-based nanocomposites 29 3.4.1 Preparation of GO/CMC hydrogel beads 29 3.4.2 Preparation of GO/CMC composite films 30 3.5 Characterizations 31 3.5.1 XRD analysis 31 3.5.2 FT-IR analysis 31 3.5.3 Raman analysis 31 3.5.4 FESEM-EDX analysis 32 3.5.5 TGA analysis 32 3.6 Swelling behavior analysis 32 3.7 Drug loading and release studies 33 3.8 In vitro cytotoxicity study 34 CHAPTER 4 RESULTS AND DISCUSSION 37 4.1 Synthesis and characterization of GO 37 4.2 Synthesis and characterization of GO/CMC and CMC Composite Material 46 4.2.1 GO/CMC and CMC hydrogel beads 46 4.2.2 GO/CMC and CMC composite films 52 4.3 Swelling behavior of hydrogel beads 56 4.4 Potential application as drug carrier 58 4.4.1 Doxorubicin loading on composite materials 58 4.4.2 Drug release of doxorubicin-loaded composite materials 60 4.4.3 In vitro cytotoxicity studies by MTT assay 62 CHAPTER 5 CONCLUSIONS & RECOMMENDATION 65 5.1 Conclusions 65 5.2 Recommendation 66 REFERENCES 67 APPENDICES 78 APPENDIX A 78 APPENDIX B 82

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