臺灣博碩士論文加值系統

奈米結構脂質載體（Nanostructured lipid carriers，NLCs）是近年來繼固體脂質奈米粒發展起來的新型載體系統。本研究探討以奈米結構脂質載體包覆維生素C棕櫚酸酯（Ascorbyl palmitate-loaded nanostructured lipid carriers，AP-NLCs）的製備及其物理化學穩定性質。選用固體脂質包括棕櫚酸鯨蠟酯、山嵛酸甘油酯及液態脂質辛酸/癸酸甘油酯，採用熱高壓均質法製備AP-NLCs，並用同法製備維生素C棕櫚酸酯-固體脂質奈米粒（Solid lipid nanoparticles，SLNs）。利用高效液相層析儀、動態光散射粒徑分析儀、界面電位測定儀及掃描式熱差分析儀；評估其包埋率與物理相關性質。並針對AP-NLCs之經皮吸收效果進行探討。
結果顯示，所有配方之平均粒徑爲250 nm以下，多分散指數（P.I）在0.3以下。AP-NLCs的包埋率皆在80%以上較AP-SLNs高。界面電位值皆高於-30mV具有良好的膠體分散狀態。DSC分析結果所有AP-NLCs的結晶度低於70%。關於AP-NLCs的穩定性評估，低溫儲存環境（4℃）可提高維生素C棕櫚酸酯的穩定性。在添加抗氧化劑對AP-NLCs穩定性影響的評估結果顯示；維生素E的效果較其它抗氧化劑佳。在儲存90天後，維生素C棕櫚酸酯之總量回收率高達65%。此外AP-NLCs添加於配方中具提高經皮吸收的效果。

Nanostructured lipid carriers （NLCs） have been developed as the new nanoparticulate delivery system in this years recently. This study is designed to investigate the preparation and physicochemical properties of Ascorbyl palmitate-loaded NLCs （AP-NLCs）. The preparation of AP-NLCs was operated by the high pressure homoenization method and solidification at low temperature. Cetyl palmitate, Glyceryl behenate and Caprylic/capric triglyceride were all chosed as lipids. AP-solid lipid nanoparticles （AP-SLNs） without the addition of Caprylic/capric triglyceride was also prepared to compare with AP-NLCs. For stability evalution, several anti-oxidant ragents were added in the AP-NLCs.
The result showed, the mean particle size, polydispersity index （P.I） of all AP- NLCs were lower than 250 nm, and 0.3, respectively. Zeta potential values higher than -30 mV were obtained indicating a good physical stability of colloidal dispersions. The encapsulation efficiency of all AP-NLCs is all above 80%. In DSC analysis, all of the AP-NLCs crystallinity was less than 70%. For the stability evalution, lower storage temperature （4℃） would increase the stability. The stability effect on the addition of several anti-oxidants was also evaluated in this study.The addition of Vitamin E showed better result than other anti-oxidants. The percentage of AP was higher than 65% after 90 days. For the percutaneous absorption study, AP-NLCs were showed better penetration effect compared with reference emulsion formulsion.

摘要 I
Abstract II
誌謝 IV
目錄 V
圖目錄 IX
表目錄 XI
第一章 緒 論 1
1-1前言 1
1-2研究背景 2
1-3研究動機及目的 4
1-4 研究架構 4
第二章　文獻回顧 7
2-1 起源 7
2-2 NLCs的種類 9
2-2-1 缺陷型（Imperfect type） 10
2-2-2 無定形型（Amorphous type） 11
2-2-3 複合型（Multiple type） 12
2-3 奈米脂質載體之製備方法 13
2-3-1 高壓勻質法 13
2-3-2溶劑揮發分散乳化法 16
2-3-4 微乳法 17
2-3-5 高速剪切均質和超音波法 18
2-3-6 W/O/W乳化法 19
2-4 奈米脂質載體的特性及應用 20
2-5皮膚的構造 22
2-5-1表皮層（Epidermis） 23
2-5-2真皮層（Dermis） 24
2-5-3皮下組織（Hypodermis） 25
2-6皮膚經皮吸收的途徑 25
第三章 實驗材料與實驗方法 29
3-1 實驗材料 29
3-2 實驗儀器 30
3-3 NLCs製備 34
3-3-1實驗之配方組成 34
3-3-2 NLCs製備方法 37
3-3-3 AP乳液之配製 37
3-4 NLCs之化學物裡穩定性評估 40
3-4-1 物理穩定性評估 40
3-4-2 化學穩定性評估 40
3-5總量回收率及包埋率之測定 41
3-5-1 總量回收率 41
3-5-2 包埋率之測定 41
3-5-3 高效液相層析儀分析 42
3-6 粒徑與界面電位之量測 43
3-6-1 粒徑之測量 43
3-6-2 界面電位之測量 43
3-7 DSC熱分析 44
3-7-1 熱分析儀 44
3-8 AP-NLCs之經皮吸收實驗 44
3-8-1 經皮吸收之皮膚的完整性測試 44
3-8-2 經皮吸收試驗 44
3-9經皮吸收樣品含量測定方式 46
3-9-1收集液分析 46
3-9-2 皮上殘餘液的收集分析 46
3-9-3 經皮吸收貼布剝除法試驗 46
3-9-4 經皮吸收豬皮的萃取分析 47
3-9-5統計及數據統整 47
第四章 結果與討論 48
4-1維生素C棕櫚酸酯NLCs之化學穩定性評估 48
4-1-1維生素C棕櫚酸酯包埋率 48
4-1-2包覆維生素C棕櫚酸酯之總量回收率 50
4-2維生素C棕櫚酸酯NLCs之物理穩定性評估 54
4-2-1 NLCs包覆維生素C棕櫚酸酯之粒徑 54
4-2-2 NLCs包覆維生素C棕櫚酸酯之界面電位 56
4-2-3掃描式熱差分析儀 58
4-3經皮吸收試驗 60
第五章 結論 62
參考文獻 83

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