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研究生:潘怡華
研究生(外文):Yi-Hua Pan
論文名稱:製備包覆18β-甘草次酸之聚硫縮酮奈米顆粒並評估其在抑制UVB誘導人類角質細胞發炎之效果
論文名稱(外文):Preparation of 18β-glycyrrhetinic acid loaded polythioketal nanoparticles and evaluation of its anti-inflammatory effect on human keratinocytes induced by UVB
指導教授:高震宇高震宇引用關係吳南霖
指導教授(外文):Chen-Yu KaoNan-Lin Wu
口試委員:高震宇吳南霖鄭智嘉
口試委員(外文):Chen-Yu KaoNan-Lin WuChih-Chia Cheng
口試日期:2019-01-14
學位類別:碩士
校院名稱:國立臺灣科技大學
系所名稱:醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:中文
論文頁數:87
中文關鍵詞:18β-甘草次酸聚硫縮酮奈米顆粒UVB活性氧物質IL-1βIL-18抑制發炎
外文關鍵詞:18β-glycyrrhetic acidpolythioketal polymernanoparticlesUVBreactive oxygen speciesIL-1βIL-18anti-inflammatory
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18β-甘草次酸(18β-glycyrrhetinic acid)是由甘草成分中的甘草甜素水解代謝後的產物,在抗發炎、抗癌、治療疾病上已有廣泛的研究,可以防止人類角質形成細胞中氧化性DNA損傷和細胞凋亡相關蛋白的激活,是有效的抗氧化劑。
硫縮酮(thioketal)是一種可以通過氧化方式降解的一種化合物,且在酸性與鹼性環境下穩定,本研究利用此種特性來包覆弱酸性的18β-甘草次酸並製備奈米顆粒。
首先,合成出聚硫縮酮高分子聚合物做為藥物載體,使用單一乳化法製備包覆18β-甘草次酸之奈米顆粒。透過UVB照射正常人類角質形成細胞(normal human keratinocyte, NHK),誘導細胞發炎產生大量活性氧物質(Reactive oxygen species, ROS),使聚硫縮酮載體降解而釋放出18β-甘草次酸。透過量測IL-1β、IL-18促炎細胞因子濃度的結果表明,包覆18β-甘草次酸之奈米顆粒有抑制發炎的效果,而18β-甘草次酸純藥濃度較高會造成較多的細胞死亡,包覆18β-甘草次酸之聚硫縮酮奈米顆粒細胞毒性較低。
18β-glycyrrhetic acid is a product of hydrolysis and metabolism of glycyrrhizin which is one of the ingredients in licorice, and it has been extensively studied in anti-inflammatory, anti-cancer and therapeutic diseases. 18β-glycyrrhetinic is potent antioxidants that prevent oxidative DNA fragmentation and the activation of apoptosis-associated proteins in human keratinocytes.
Thioketal is a compound that can be degraded selectively in response to reactive oxygen species (ROS) and is stable in acidic and alkaline environments. This study used this property to coat 18β-glycyrrhetinic acid to prepare nanoparticle.
First, the polythioketal polymer was synthesized as a drug carrier, and the nanoparticle coated with 18β-glycyrrhetic acid was prepared by a single emulsification method. Normal human keratinocyte (NHK) is irradiated by UVB to induce inflammation and release a large amount of reactive oxygen species (ROS), which degrades the polythioketal carrier and releases 18β-glycyrrhetic acid. The results of measuring the concentration of IL-1β and IL-18 proinflammatory cytokines showed that the nanoparticle coated with 18β-glycyrrhetinic acid had the effect of inhibiting inflammation. However, the higher concentration of 18β-glycyrrhetinic acid pure drug caused more death cell, and the polythioketal nanoparticle coated with 18β-glycyrrhetinic acid had lower cytotoxicity.
摘要 I
Abstract II
致謝 III
目錄 IV
圖目錄 VII
表目錄 X
縮寫表 XI
第一章 緒論 1
第二章 文獻回顧 3
2.1 皮膚組織結構 3
2.1.1 表皮角質形成細胞(Keratinocyte) 5
2.2 紫外線 6
2.1.2 紫外線對皮膚的影響 7
2.2.1 活性氧物質(Reactive oxygen species, ROS)與自由基 8
2.3 藥物傳輸系統(Drug delivery system, DDS) 9
2.3.1 高分子材料載體 11
2.3.2 高分子聚合物奈米顆粒載體製備 12
2.4 硫縮酮(Thioketal) 14
2.5 甘草(Glycyrrhiza uralensis, Licorice) 15
2.5.1 18β-甘草次酸(18β-glycyrrhetinic acid) 16
第三章 研究設計與材料方法 17
3.1 研究設計 17
3.1.1 實驗設計 17
3.1.2 實驗架構與流程 19
3.2 實驗藥品、試劑與儀器設備 20
3.2.1 實驗藥品試劑 20
3.2.2 細胞培養用之藥品試劑 20
3.2.3 實驗分析儀器設備 21
3.3 PPADT高分子聚合物合成 23
3.4 PPADT高分子聚合物特性分析 24
3.4.1 PPADT高分子聚合物組成分析 24
3.4.2 PPADT高分子聚合物分子量分析 25
3.5 奈米顆粒載體製備 26
3.5.1 PPADT-blank NPs製備 26
3.5.2 PPADT-18β-GA NPs製備 26
3.5.3 PPADT-Nile red NPs製備 27
3.6 奈米顆粒載體特性分析 28
3.6.1 粒徑分析 28
3.6.2 表面型態觀察 28
3.6.3 藥物包覆率分析 29
3.6.4 釋放效率 30
3.7 體外細胞實驗 31
3.7.1 細胞培養 31
3.7.2 細胞培養培養液配製 33
3.7.3 細胞繼代培養 33
3.7.4 細胞計數 34
3.7.5 UVB誘導細胞發炎 34
3.7.6 細胞毒性MTT assay 35
3.7.7 PPADT-18β-GA NPs抗發炎效果分析 36
第四章 結果 37
4.1 PPADT高分子聚合物特性分析 37
4.1.1 PPADT高分子聚合物組成分析 37
4.1.2 PPADT高分子聚合物分子量分析 39
4.2 奈米顆粒載體特性分析 41
4.2.1 粒徑分析 41
4.2.2 顆粒表面型態觀察 44
4.2.3 藥物包覆率分析 48
4.2.4 釋放效率 50
4.3 細胞實驗 51
4.3.1 細胞型態觀察 51
4.3.2 細胞毒性MTT assay 56
4.3.3 PPADT-18β-GA NPs顆粒抗發炎效果 59
第五章 討論 62
5.1 PPADT高分子聚合物特性分析 62
5.2 PPADT-blank NPs與PPADT-18β-GA NPs特性分析 62
5.3 細胞體外實驗評估 63
第六章 結論 64
未來展望 64
參考文獻 65
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