| 摘要: |
| 目的考察微针对熊果苷皮肤给药的促渗作用,并与化学促渗剂氮酮进行比较。方法采用深反应离子刻蚀技术制备星形硅微针。制备熊果苷水凝胶剂,采用Franz扩散池法,将人体腹部皮肤置于扩散池间,分3组:微针实验组供给室加入熊果苷水凝胶,皮肤采用微针作用；氮酮对照组供给室分别加入含有1%、3%、5%氮酮的熊果苷水凝胶,皮肤无微针作用；空白对照组供给室加入无氮酮熊果苷水凝胶,皮肤无微针作用。分别在1、3、6、12、24、36、48 h等时间点取样,以HPLC法测定接收池、皮肤表皮层和真皮层中的熊果苷含量,液相条件: C18柱(250 mm×4.6 mm,5 μm)；流动相为甲醇1×10-3mol/ml盐酸(595)；柱温25℃；流速1 ml/min；检测波长282 nm。求算熊果苷的累积透过量(Qr)、稳态透皮速率(Js)及皮肤累积滞留量(Qs)。结果星形硅微针可以刺穿人体皮肤角质层。HPLC标准曲线方程C=0.000 2A-0.182 9 (r=0.999 9),线性范围0.4～50 μg/ml、日内精密度和日间精密度分别为2.4%和2.74%,回收率均大于90%。微针作用组的熊果苷累计透过量、稳态透皮速率和表皮累计滞留量均高于5%氮酮组(P＜0.01)。结论 微针作用皮肤后可显著增加熊果苷皮肤渗透量。 |
| 关键词: 微针 熊果苷 氮酮 皮肤投药 |
| DOI：10.3724/SP.J.1008.2011.080 |
| 投稿时间：2010-07-05修订日期：2010-11-25 |
| 基金项目:国家自然科学基金(81000689), 上海市自然科学基金(10ZR1437300), “重大新药创制”科技重大专项(2008ZXJ09010-001). |
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| Microneedle technique in promoting transdermal delivery of arbutin |
| ZHANG Wei1,GAO Jing2,ZHANG Min1,WU Xin1,HOU Xue-mei1,GAO Shen1* |
| (1. Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;;2. Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| ObjectiveTo study the promoting effects of microneedle arrays on transdermal delivery of arbutin by comparing with the effect of chemical penetration enhancer azone. MethodsThe microneedles were fabricated with singlecrystal Si as starting material using a series of photolithography, thinfilm deposition, and reactive ion etching techniques. Franzcells were used in the transdermal delivery experiment with human abdominal skin. The study was divided into the following 3 groups: the microneedle group (arbutin hydrogel without penetration enhancer, and the skin was treated with microneedle arrays); the control group (arbutin hydrogels containing 1%, 3%, and 5% azone (W/V), and the skin received no microneedle treatment); and blank control group (arbutin hydrogel without azone, and the skin received no microneedle treatment). Arbutin levels in the receptor solution, epidermis and dermis were determined by HPLC at 1, 3, 6, 12, 24, 36 and 48 h. The analyses were performed with a C18 column (250 mm×4.6 mm, 5 μm), at room temperature, mobile phase methanol1×10-3mol/ml HCl solution (V/V, 595), flow rate 1 ml/min, and detective wavelength 282 nm. The accumulative penetration amount(Qr), steadystate flux(Js) and the accumulative deposition amount(Qs)were calculated. ResultsThe microneedles could pass the human skin. The standard curve was: C=0.000 2A-0.182 9 (r=0.999 9), 0.450 μg/ml. The RSD values of intraday and interday precisions were 2.4% and 2.74%, respectively; and the recovery was higher than 90%.The values of Qr, Js, and Qs in the microneedle group were significantly higher than those in the 5% azone group(P＜0.01). Conclusion Microneedles can greatly promote the skin permeability and deposition of arbutin. |
| Key words: microneedles arbutin azone cutaneous administration |
