Effects of microneedle-roller insertion times on skin permeation characteristics,drug distribution and skin irritation
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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。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.
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Key words:
- microneedle-roller /
- insertion times /
- permeation characteristics /
- skin irritation /
- tretinoin
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[1] 占浩慧,黄颖聪,马凤森.微针穿刺性能评价方法研究进展[J].中国药学杂志,2018,53(22):1890-1895. [2] 李雅,张娟娟,张立超,等.改装滚轮微针促进人增生性瘢痕皮肤对醋酸曲安奈德的吸收[J].第二军医大学学报,2015,36(1):58-64. [3] 张娟娟,张立超,朱全刚,等.改装滚轮微针用于醋酸曲安奈德经皮给药的特性试验[J].中国医院药学杂志,2015,35(4):292-296. [4] ZHOUC P,LIU Y L,WANG H L,et al.Transdermal delivery of insulin using microneedle rollers in vivo[J].Int J Pharm,2010,392(1-2):127-133. [5] YOONJ,PARK D,SON T,et al.A physical method to enhance transdermal delivery of a tissue optical clearing agent:combination of microneedling and sonophoresis[J].Lasers Surg Med,2010,42(5):412-417. [6] BADRAN M M,KUNTSCHE J,FAHR A.Skin penetration enhancement by a microneedle device (Dermaroller) in vitro:dependency on needle size and applied formulation[J].Eur J Pharm Sci,2009,36(4-5):511-523. [7] YOUS K,NOH Y W,PARK H H,et al.Effect of applying modes of the polymer microneedle-roller on the permeation of L-ascorbic acid in rats[J].J Drug Target,2010,18(1):15-20. [8] 张娟娟,朱全刚,张立超,等.不同密度滚轮微针对维A酸经皮渗透的影响[J].药学服务与研究,2013,13(6):440-444. [9] 张娟娟.力度可控性滚轮微针的构建及其对大面积皮肤药物吸收影响研究[D].宁夏:宁夏医科大学,2014. [10] 鞠强.维A酸类药物在痤疮治疗中的应用[J].皮肤病与性病,2018,40(1):26-28. [11] WANG Q,JAIMES-LIZCANO Y A,LAWSON L B,et al.Improved dermal delivery of FITC-BSA using a combination of passive and active methods[J].J Pharm Sci,2011,100(11):4804-4814. -
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