以油狀懸浮法與微脂粒促進熊果酸經皮輸送之研究

Enhancement of the transdermal delivery of ursolic acid by oil- suspension and liposome methods.

黃毓瑾(Yu-Chin Huang)

指導教授 ： 陳志成

大同大學/工程學院/生物工程學系所/碩士(2007年)

摘要

本實驗利用微脂粒包覆熊果酸(Ursolic acid, URA) 以及添加不同的經皮吸收增加劑(penetration enhancer)評估藥物經皮傳遞的促進效果。微脂粒的配方包含磷脂質(phospholipid)之二棕櫚醯磷脂醯膽鹼(Dipalmitoylphosphatidylcholine, DPPC)與蛋黃卵磷脂(Egg-yolk L-α-Phosphatidylcholine, EYPC)或是含界面活性劑如去氧膽酸(Deoxycholic acid, DA ) 、十八烷基胺(Stearylamine, SA)與己六醇油酸酯(Sorbitan monooleate, Sp80)，以及利用橄欖油及豬油製作油狀懸浮液。藉著Franz-type擴散槽進行皮膚穿透實驗，得知各配方的皮膚穿透係數。藉由螢光探針標的微脂粒的結構進行螢光光譜儀分析。由螢光偵測得知，若與添加SA來比較，則添加DA與Sp80於微脂粒中會影響脂雙層排列而使微脂粒具有較易穿透之性質。包覆3 mM熊果酸之微脂粒(只含EYPC)其皮膚穿透係數為0.025 ±0.002 cm/hr，未經微脂粒包覆之熊果酸溶液，其皮膚穿透係數為0.017 ±0.001 cm/hr，顯示微脂粒包覆對於藥物具有促進輸送作用。包覆不同熊果酸濃度實驗中可得知，熊果酸皮膚穿透係數隨濃度增加而上升。使用EYPC或DPPC(不含界面活性劑)製作微脂粒的實驗中，發現皮膚穿透係數無顯著差異。添加不同界面活性劑實驗中，以添加DA配方之皮膚穿透係數最佳達到0.042 ±0.002 cm/hr。若與添加SA來比較，則後者之皮膚穿透係數，只有0.022 ±0.002 cm/hr。所以由螢光探針所發現的結果，若其微脂粒有較易穿透性質者，其皮膚穿透係數也較高。而在製作油狀懸浮液之穿皮實驗中，發現以DA、豬油與EYPC製作熊果酸油狀懸浮液的實驗中，可獲得最高皮膚穿透係數至0.049 ±0.002 cm/hr。所以油狀懸浮液比微脂粒有更佳的藥物穿皮效果。

關鍵字

微脂粒 ； 皮膚穿透係數 ； 經皮傳遞 ； 油狀懸浮液 ； 熊果酸

並列摘要

The ursolic acid encapsulated by liposome and different penetration enhancer was used to evaluate the improving effects for the drug transdermal delivery. The formulations for liposome included phospholipids such as egg-york L-α-Phosphatidylcholine (EYPC), and dipalmitoylphosphatidylcholine (DPPC). The enhancer included surfactants like deoxycholic acid (DA), stearylamine (SA), and Sorbitan monooleate (Sp80). Besides, we also used olive oil and lard to prepare oil-suspension for ursolic acid. To measure the permeability coefficient of ursolic acid under different formulations, we used the Franz-type diffusion cell to perform the transdermal penetration test. Furthermore, fluorospectrometer analysis was designed to evaluate the penetration ability of liposome by a fluorescent probe. Comparing different surfactant incorporating DA and Span80 into liposome affected the lipid-bilayer arrangement and made liposome more penetrable. The permeability coefficient of transdermal delivery for the ursolic acid(3 mM) encapsulated by liposome (containing EYPC only) was 0.025 ±0.002 cm/hr, but the permeability coefficient of the ursolic acid unencapsulated by liposome was only 0.017 ±0.001 cm/hr. The result indicates that the encapsulation of liposome promotes the drug delivery. The transdermal permeability coefficient will increase along with the increasing concentration of encapsulated ursolic acid. As a result, the transdermal permeability coefficient for the liposome which included EYPC or DPPC (containing no surfactant) did not show the significant differences. By incorporating DA into liposome, the permeability coefficient will reach as high as 0.042 ±0.002 cm/hr. If we compare DA with SA, the permeability coefficient of ursolic acid in liposome of SA is only 0.022 ±0.002 cm/hr. Therefore, a better penetrability of liposome by the fluorescent probe also show a higher permeability coefficient of ursolic acid encapsulated by such liposome. The oil suspension of ursolic acid in DA and lard had the highest permeability coefficient of 0.049 ±0.002 cm/hr. Therefore, oil-suspension shows a better drug transdermal delivery than liposome.

並列關鍵字

transdermal delivery ； oil-suspension ； liposome ； ursolic acid ； permeability coefficient

參考文獻

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