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研究生:楊孫瑜
研究生(外文):Sun-Yu Yang
論文名稱:以多重乳化技術建構奈米脂質載體提升植化素之經皮吸收
論文名稱(外文):Development of a W/O/W type Nanostructured Lipid Carrier System to Enhance Percutaneous Absorption of Phytochemicals
指導教授:蔣丙煌蔣丙煌引用關係
口試日期:2017-07-17
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:食品科技研究所
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:89
中文關鍵詞:多重乳化技術奈米結構脂質載體田口法反應曲面法閉鎖效應經皮給藥系統
外文關鍵詞:Multiple emulsification techniqueNanostructured lipid carriersTaguchi methodResponse Surface MethodologyOcclusion effectTransdermal delivery system
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自然界有許多植物含有豐富的抗氧化物質,這些抗氧化物可有效降低自由基對細胞的傷害,進而阻止皮膚的老化,因此市面上許多護膚品都以植物萃取物作為重要配方成分。然而,不論是外用藥膏或是保養品,這些成分都需透過適當的載體包覆技術,才能穿透皮膚表面緻密的角質層,到達其發揮作用的位置。本實驗結合多重乳化技術與奈米結構脂質載體的概念,製作一粒徑大小介於 50 ~ 500 nm ,可同時搭載親脂性與親水性植化素的 W/O/W type 奈米脂質顆粒,藉由評估其載藥能力、 促經皮穿透率等特性,來優化該載體的組成,以期應用於提升各類活性物質對皮膚的保健功效。實驗初期以田口法及反應曲面法篩選製程中的重要變因,並取得相關變數的回歸方程式。結果發現,為尋求多重乳化液的穩定,須同時考量載體中的內水相W1比例與界面活性劑Span 80、Tween 80的添加量,進而得到粒徑小且物質包覆率高的載體;將上述優化的載體配方進行經皮吸收試驗,與控制組溶液相比後則得到促進比值。結果顯示,所製備的載體確實可以促進活性物質的經皮穿透,且其中以粒徑最小的配方 (102.2 ± 18.7 nm) 具最顯著的效果,推測原因為奈米大小的載體有利於在皮膚表層形成閉鎖效應,提高皮膚的保水量而寬廣化親水性通道,使得物質的經皮滲透性得以有效提升。為評估載體應用於經皮吸收系統的安全性及穩定性,分別以儲藏安定性試驗、細胞毒性測試及經皮穿透後的H&E染色切片來加以測定。使用人類真皮纖維母細胞進行細胞毒性測試,發現載體內含的親脂性界面活性劑Span 80,會與細胞膜的疏水區域作用而對細胞造成破壞。然而,皮膚切片的結果則顯示載體對整體皮膚結構並無明顯損害。另外,載體即使經歷反覆的冷凍解凍循環後,仍展現了良好的儲存安定性,未發生液滴聚集或活性物質大量損失的情況。因此推論,本次實驗所製備的W/O/W type奈米脂質載體,能夠以安全穩定又有效的形式應用於經皮給藥系統。
Various plant extracts exhibit strong antioxidant activities that can effectively reduce free radical damage, therefore could be used as anti-aging agent for topical cosmetics. However, it is well known that the stratum corneum, the outermost layer of the skin, constitutes an dense barrier to substances, pose a major difficulty for the transdermal delivery system. Therefore, it is necessary to construct an appropriate carrier to protect the internal active ingredients from deterioration and enhance its percutaneous absorption. The aim of this study was to combine the concepts of multiple emulsification technique and nanostructured lipid carriers to develop a W/O/W type nano-lipid particle system, which can encapsulate both lipophilic and hydrophilic phytochemicals with particle size distribution ranged from 50 to 500 nm. To optimize the composition of this carrier, we used Taguchi method and Response Surface Methodology as tools to get proper quadratic polynomial models, and used smaller size and higher encapsulation efficiency as desired functions. Results showed that the formulation with the lowest particle size had the highest enhancement ratio of permeation, most likely due to the occlusion effect of nano-size on skin hydration. Furthermore, cytotoxicity on skin fibroblast, histological appearance of skin and storage stability of carriers were evaluated. Results showed that the W/O/W type nano-lipid particle system posed limited risks to human skin. In addition, the system can remain stable after repeated Freeze-thaw cycles. In conclusion, the carrier system developed in this study is a safe and effective vehicle for transdermal delivery of phytochemicals.
謝誌 i
中文摘要 ii
英文摘要 iii
目錄 iv
附圖目錄 vi
圖目錄 vii
表目錄 ix
第一章、文獻回顧 1
一、多重乳化液 (Multiple emulsions) 1
(一) 多重乳化液之簡介 1
(二) 多重乳化液的製備 – 以W/O/W type emulsion為例 2
(三) 多重乳化液的穩定性 3
(四) 多重乳化液的應用 8
二、 奈米結構脂質載體 (Nanostructured lipid carriers) 11
(一) 簡介 11
(二) 常用製備方法 12
(三) 優點與應用 13
三、 經皮給藥系統(Transdermal delivery system) 14
(一) 簡介 14
(二) 人體皮膚構造 15
(三) 藥物穿透皮膚之途徑 16
(四) 影響藥物經皮吸收之因子 17
(五) 經皮促滲透劑 (Penetration Enhancer) 18
(六) 經皮穿透的評估模式 20
四、 應用於皮膚保健之活性物質 21
(一) 光老化 (Photo-aging) 21
(二) 自然界具光保護效果之活性成分 21
第二章、研究目的與實驗架構 23
一、 實驗目的 23
二、 實驗架構 24
第三章、材料與方法 25
一、 實驗材料 25
(一) 載體成分 25
(二) 實驗用動物 25
(三) 實驗細胞株 25
(四) 其他實驗藥品與試劑 25
(五) 實驗器材與儀器 26
二、 實驗方法 26
(一) 載體製備及初步特性分析 26
(二) 優化載體組成 30
(三) 經皮吸收試驗 35
(四) 載體之細胞毒性測試 37
(五) 載體之物化特性評估 39
第四章、結果與討論 40
一、 W/O/W type奈米脂質載體之組成優化 40
(一) 固體脂質與液態油脂組成比例之篩選 40
(二) 基質油之DSC示熱差掃描儀測定 42
(三) 田口參數重要性分析 43
(四) 建構反應曲面方程式 49
二、W/O/W type奈米脂質載體促進物質經皮吸收之效果 65
(一) 活性物質之經皮穿透累積量 65
(二) 活性物質於皮膚之滯留量 69
三、 W/O/W type奈米脂質載體對皮膚的可能影響 71
(一) 優化載體之細胞毒性測試 71
(二) 優化載體對於皮膚組織之影響 73
四、 W/O/W type奈米脂質載體之物化特性評估 75
(一) W/O/W type奈米脂質載體之型態 75
(二) W/O/W type奈米脂質載體之存放安定性 77
第五章、結論 82
第六章、參考文獻 83
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