滚轮微针处理次数对药物皮肤渗透、分布及皮肤刺激性的影响
投稿时间:2019-03-03  修订日期:2019-04-28  点此下载全文
引用本文:张娟娟,傅翔,朱全刚,张立超.滚轮微针处理次数对药物皮肤渗透、分布及皮肤刺激性的影响[J].药学实践杂志,2019,37(5):416~421
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作者单位E-mail
张娟娟 上海市中医医院药剂科, 上海 200071
上海市浦东新区新场社区卫生服务中心, 上海 201314 
 
傅翔 上海市控江医院药剂科, 上海200093  
朱全刚 上海市皮肤病医院药剂科, 上海200443  
张立超 上海市中医医院药剂科, 上海 200071 changhaiskin@163.com 
基金项目:上海市卫计委科研项目(201540294);浦东新区科技发展基金(PKJ2016-Y23)
中文摘要:目的 考察用于皮肤促透研究的滚轮微针处理次数。方法 以维A酸为模型药物,Franz扩散池、组织匀浆法研究裸鼠皮肤的促透效果,用亚甲蓝染色法、激光共聚焦显微镜法等考察裸鼠皮肤的药物分布,经皮水分流失(TEWL)测量法、激光多普勒血流量法评价皮肤刺激性。结果 滚轮微针处理次数为1、3、5、8、10次时,处理次数越多,促透效果越好,皮肤中滞留药量也越高,但是皮肤中滞留药量在处理8次和10次时无显著性差异(P>0.05)。亚甲基蓝染色和激光共聚焦实验均显示处理次数增加,针孔分布均匀度提高;亚甲基蓝染色显示,处理5次以上时,出现部分针眼重叠而皮肤破损现象。在体皮肤内药物吸收实验显示处理1次时,裸鼠皮肤中滞留药量均匀性较差,但是处理3次以上时,皮肤中滞留药量均匀性明显改善。TEWL测量法显示处理5次以下,皮肤屏障功能恢复时间为24 h,处理8次以上为36 h。激光多普勒血流量法显示处理5次以下,皮肤屏障功能恢复时间为1 h,处理8次以上为2 h。结论 滚轮微针处理5次可确保裸鼠皮肤促透研究的安全性和有效性。
中文关键词:滚轮微针  处理次数  渗透特性  皮肤刺激性  维A酸
 
Effects of microneedle-roller insertion times on skin permeation characteristics,drug distribution and skin irritation
Abstract:Objective To study the effects of microneedle-roller insertion times on skin permeation.Methods Tretinoin was used as model drug.The in vitro transdermal characteristics in nude mice were studied with Franz diffusion cell and the tissue homogenization method.The drug distribution in nude mice skin was investigated by methylene blue staining and confocal lasers scanning microscope.The skin irritation was evaluated by trans-epidermal water-loss (TEWL) measurement and laser Doppler flowmetry.Results Within the microneedle roller insertion times 1,3,5,8,and 10,the better penetration effect and drug accumulation in skin were achieved with the increment of insertion times.However,there was no significant difference in the skin accumulation between 8 and 10 times of the insertion(P>0.05).The results from methylene blue staining and microscope confocal lasers scanning indicated that the uniformity of needle hole distribution was increased with the increased insertion times.However,some needle hole overlap and skin damages were observed from methylene blue staining when insertion times were more than five.The in vivo drug absorption study indicated that the drug accumulation was inhomogeneous in nude mice skin after one treatment.It was significantly improved after three treatments.The results from TEWL measurements suggested that the recovery time of skin barrier function was 24 hours if insertion was less than five times and 36 hours if more than eight times.The results of laser Doppler flowmetry indicated that the recovery time of skin barrier function was 1 hour if insertion times were less than five,and 2 hours if more than eight times.Conclusion The optimal microneedle insertion time was five times,which could ensure the safety and effectiveness of the skin permeation study in nude mice.
keywords:microneedle-roller  insertion times  permeation characteristics  skin irritation  tretinoin
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