含DHDAB微脂粒的物化性質、藥物包覆與皮膚穿透行為及混合磷脂質/DHDAB單分子層的特徵

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Title:	含DHDAB微脂粒的物化性質、藥物包覆與皮膚穿透行為及混合磷脂質/DHDAB單分子層的特徵 Physicochemical properties, drug encapsulation and skin permeation behavior of liposomes containing DHDAB and characterization of mixed phosphatidylcholine/DHDAB monolayers
Authors:	陳蕙萍
Contributors:	周宗翰嘉南藥理科技大學：化妝品科技研究所
Keywords:	單分子層維生素E 經皮穿透微脂粒物化性質 liposome physicochemical properties monolayer skin permeation vitamin E
Date:	2009
Issue Date:	2010-03-30 14:22:04 (UTC+8)
Abstract:	本研究主要探討氫化大豆飽和磷脂質(hydrogenated soybean phosphatidylcholine, HSPC)與不飽和卵磷脂(egg phosphatidylcholine, EPC)分別添加膽固醇(cholesterol, CHOL)與雙十六烷基二甲基溴化銨(dihexadecyldimethylammonium bromide, DHDAB)所形成微脂粒的物化性質。量測微脂粒粒徑與界面電位分佈，並觀察室溫及4℃下兩種物理特徵隨時間的變化。並針對混合HSPC/CHOL、EPC/CHOL、HSPC/DHDAB及EPC/DHDAB所形成的微脂粒，進行螢光偏極化特性的分析，發現膽固醇及DHDAB的添加都會對飽和磷脂質微脂粒脂雙層膜內分子排列失序，但膽固醇的添加會使不飽和卵磷脂微脂粒脂雙層膜內分子排列比較有秩序性。而DHDAB的加入對不飽和卵磷脂微脂粒脂雙層膜內分子結構並無顯著影響。根據微脂粒物理穩定性的結果，選用穩定性佳的微脂粒組成進行包覆複合物A的實驗，以了解微脂粒包覆疏水性藥物的行為。除此之外，藉由Franz垂直擴散槽進行微脂粒包覆複合物A體外經皮吸收的試驗，以評估利用微脂粒包覆複合物A，藥物穿透皮膚的效果。得知帶負電微脂粒包覆複合物A經皮穿透效果最佳。在24℃下，分別進行混合 HSPC/DHDAB 及混合 EPC/DHDAB 單分子層表面壓-每分子佔據面積(-A)等溫線之量測。根據 -A等溫線結果分別顯示 HSPC 與 DHDAB 和 EPC 與 DHDAB 在24℃下氣/液界面上是可以互相混合的。此外，再進行固定表面壓 30 mN/m下，面積鬆弛行為，發現 HSPC 與 EPC 添加越多 DHDAB 的混合單分子層會呈現較具動態的不穩定性。並藉由螢光顯微鏡(fluorescence microscopy)觀察混合HSPC/DHDAB 單分子層，發現隨著 DHDAB 的添加或表面壓的增加並沒有明顯的凝縮區域(condensed domains)存在。並進一步針對微脂粒與混合單分子層的行為關聯性也進行討論。 In a study work, physicochemical properties of liposomes of hydrogenated soybean phosphatidylcholine (HSPC) and egg phosphatidylcholine (EPC) adding cholesterol (CHOL) and dihexadecyldimethylammonium bromide (DHDAB) are investigated. Particle size distribution and zeta potential of liposomes were measured and were recorded with time at room temperature and 4℃ storage. Mixed HSPC/CHOL, EPC/CHOL, HSPC/DHDAB and EPC/DHDAB liposomes carried out fluorescence polarization examination to study effects of CHOL and DHDAB on molecular arrangement of the lipid bilayer. The stable liposomal formulation was selected to encapsulate compound A in order to understand behavior of encapsulating hydrophobic drugs by liposomes. In addition, Franz-type diffusion cells were used to perform in vitro skin permeability for evaluating skin penetration efficiency of liposome- compound A. Surface pressure–per molecular area (-A) isotherms of mixed HSPC/DHDAB and mixed EPC/DHDAB monolayers at the air/water interface were measured at 24℃. The results showed that mixed HSPC/DHDAB and mixed EPC/DHDAB monolayers were miscible at the air/water interface at 24℃. Furthermore, area relaxation curves fixed at 30 mN/m expressed that adding DHDAB into phosphatidylcholine (PC) monolayer make mixed systems unstable kinetically. Fluorescence microscopy was utilized to directly observe morphology of mixed HSPC/DHDAB monolayer. No condensed domains were found as addition of DHDAB into HSPC monolayer or compressing with increasing surface pressures. The behavior of liposomes correlated with mixed monolayer are also discussed in this study.
Relation:	校內校外均不公開，學年度：97，172頁
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