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標題: | 奈米級d-limonene/水乳化液之製備及其皮膚穿透效果 D-limonene-in-water nanoemulsions preparation and its skin permeation performance |
作者: | Po-Hsien Li 李柏憲 |
指導教授: | 蔣丙煌(Been-Huang Chiang) |
關鍵字: | 奈米級乳化液,超音波乳化技術,d-limonene,反應曲面模式,奧斯瓦老化,經皮吸收系統,薑黃素, Nanoemulsions,Ultrasonic emulsification,d-limonene,Response surface methodology,Ostwald ripening,Transdermal delivery system,Curcumin, |
出版年 : | 2011 |
學位: | 博士 |
摘要: | 本研究為利用混合界面活性劑Span 85和 Brij 97配合超音波乳化技術來製備d-limonene奈米級乳化液,試驗設計以反應曲面模式來探討製程之最適化條件,結果顯示So ratio為0.6-0.7、應用功率18 W,在乳化時間120秒時可以得到粒徑小於100 nm之奈米級乳化液。乳化液起始pH值為6.4時,此時表面電位為-20 mV,在pH值4.0時電位接近0 mV; 而在pH值12.0值電位接近-30 mV。由TEM觀察顯示,奈米級乳化液中液滴顆粒呈現圓球狀,中心陰影部份為d-limonene包覆在乳化系統中。奈米級乳化液最主要的不安定現象為奧斯瓦老化,老化速率在25oC (0.39 m3s-1x1029)時會較4oC (1.44 m3s-1x1029)來的低,此結果與LSW理論符合。儘管奧斯瓦老化是影響奈米級乳化液安定性最主要的因子,但是貯藏試驗果顯示,經過八週的d-limonene奈米級乳化液仍然安定。法蘭茲擴散器可以用來評估d-limonene奈米級乳化液通透老鼠腹部皮膚之效果,越小之液滴通透效率越好,最高的通透速率為液滴粒徑大小為54 nm。在6小時的皮膚通透試驗顯示,d-limonene在皮膚中的濃度可達40.11 µg/cm2,由組織切片的照片可以觀察到,皮膚並無明顯之孔洞與間隙,顯示d-limonene奈米級乳化液當作藥物經皮吸收傳遞系統的安全性。此外,奈米級乳化液有促進薑黃素經皮膚吸收效果,載體液滴粒徑越小,穿透效果越好。 D-limonene in water nanoemulsion was prepared by ultrasonic emulsification using mixed surfactants of sorbitane trioleate and polyoxyethylene (20) oleyl ether. Investigation using response surface methodology revealed that 10% d-limonene nanoemulsions formed at So ratio (d-limonene concentration to mixed surfactant concentration) 0.6-0.7 and applied power 18 W for 120 s had droplet size below 100 nm. The zeta potential of the nanoemulsion was approximately -20 mV at original pH 6.4, closed to zero around pH 4.0, and around -30 mV at pH 12.0. TEM examination showed that the droplets are spherical and the gray parts of the droplets are d-limonene precipitation incorporated in spherical droplets of the emulsion system. The main destabilization mechanism of the systems is Ostwald ripening. The ripening rate at 25oC (0.39 m3s-1x1029) was lower than that at 4oC (1.44 m3s-1x1029), which was in agreement with the LSW theory. Despite of Ostwald ripening, the droplet size of d-limonene nanoemulsion remained stable after 8 weeks of storage. Franz diffusion cells were used to evaluate the permeation of d-limonene nanoemulsion through the rat abdominal skin, and the permeation rate was found to be size dependent. The maximum permeation rate was achieved by the emulsion with the lowest droplet size (54 nm). The concentration of d-limonene in the skin reached 40.11 µg/cm2 after 6 h. The histopathological photograph showed that there was no obvious void and empty space in the epidermal region, indicating that the D-limonene nanoemulsion is a safe carrier for transdermal drug delivery. Furthermore, d-limonene nanoemulsions can enhance the transdermal delivery of curcumin, and the smaller the droplet size of the carrier, the higher the permeation rate through rat skin. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35173 |
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顯示於系所單位: | 食品科技研究所 |
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