柚皮素奈米載體之局部經皮吸收評估

Study of naringenin-loaded nanoparticle carrier in topical drug delivery

方志文(Chih-Wun Fun)

指導教授 ： 吳寶珠

高雄醫學大學/藥學院/藥學研究所/碩士(2014年)

摘要

Naringenin為類黃酮化合物，能誘導黑色素酶、移除自由基。幫助皮膚生成能吸收紫外線的黑色素，也能阻擋紫外線照射產生的自由基傷害，減少皮膚光老化的發生。但Naringenin溶解度不佳，生體可用率低，對於藥物代謝的phase I與phase II的酵素都有影響，在口服使用上有諸多限制，所以本實驗擬藉由經皮給藥方法來增加Naringenin的可用性。實驗中利用奈米載體：微乳劑、微脂粒及固態脂質奈米粒來包埋Naringenin。並進行劑型的物化性質評估，體外穿皮試驗評估，及製劑安定性評估，以了解奈米載體對藥物的經皮累積穿透量及皮膚沈積量之影響並評估製劑可用性。由結果：微乳劑處方ITSP-12，平均粒徑約為0.67 nm，黏度為116.17 cPs，具有不錯的經皮累積穿透量及皮膚沈積量。而微脂粒處方FD4，平均粒徑約為123.67 nm，表面電荷為-11.00，一樣擁有不錯的皮內沈積量，但經皮累積穿透量較低。ITSP-12與FD4在安定性結果均顯示具有一定的穩定性。

關鍵字

柚皮素 ； 微乳劑 ； 微脂粒 ； 固態脂質奈米粒 ； 經皮吸收

並列摘要

Naringenin (5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) is a flavanone compound. It can increase melanogenic enzymes and remove free radical. Hence, it can protect skin from free radical damaging. But Naringenin is insoluble in water and low bioavailability which limited its oral utility. Hence, the transdermal drug delivery system might be an potented administration route. In this study, nanoparticle carriers including microemulsion, liposome, and SLN were used as carriers to transprt naringenin. The physicochemical properties, in vitro skin permeation and stability of drug-loading carriers were evaluated. ITSP-12 was a microemulsion formulation. Its particle size and viscosity were 0.67 nm and 116.17 cPs, respectively. It had higher skin permeation amount and higher disposition amount in skin. FD4 was liposome formulation. Its particle size was 123.67 nm and zeta potential was -11.00. In comparison with ITSP-12, FD4 showed higher total disposition amount in skin and lower permeation amount, indicated that liposome might be a potential carrier for tapocal application of naringenin.

並列關鍵字

Naringenin ； Microemulsion ； Liposome ； Solid lipid nanoparticle ； Transdermal drug delivery

參考文獻

1. UV index history data. 2014. http://www.cwb.gov.tw/V7e/observe/UVI/UVI_Hist.htm.)

2. UVI forecast. 2014. http://taqm.epa.gov.tw/taqm/en/UvForcast.aspx.)

3. Huang YC, Yang CH, Chiou YL. Citrus flavanone naringenin enhances melanogenesis through the activation of Wnt/beta-catenin signalling in mouse melanoma cells. Phytomedicine 2011;18:1244-9.

4. Felgines C, Texier O, Morand C, Manach C, Scalbert A, Regerat F, Remesy C. Bioavailability of the flavanone naringenin and its glycosides in rats. Am J Physiol Gastrointest Liver Physiol 2000;279:G1148-54.

5. Shulman M, Cohen M, Soto-Gutierrez A, Yagi H, Wang H, Goldwasser J, Lee-Parsons CW, Benny-Ratsaby O, Yarmush ML, Nahmias Y. Enhancement of naringenin bioavailability by complexation with hydroxypropyl-beta-cyclodextrin. PloS one 2011;6:e18033.