蒿甲醚可溶解微针透皮贴片的制备和评价  

Preparation and Evaluation of Artemether-Loaded Dissolving Microneedles

作　　者：邱玉琴[1] 李春[1,2] 张锁慧[1] 杨国忠[1,2] 贺美琳[1,2] 高云华[1] 

机构地区：[1]中国科学院理化技术研究所光化学转换和功能材料重点实验室,北京100190 [2]中国科学院大学,北京100049

出　　处：《今日药学》2016年第8期532-537,共6页Pharmacy Today

基　　金：国家自然科学基金项目(31300763)

摘　　要：目的蒿甲醚(artemether,ARM)是具有强抗疟活性的青蒿素衍生物,但其难溶于水,口服生物利用度低,有效血药浓度维持时间短。本研究的目的是开发一种能够克服现有蒿甲醚制剂缺点的可溶解微针透皮贴片。方法本文制备了ARM可溶解微针透皮贴片,评价其吸湿性、稳定性、皮肤穿透性、体内外释药性。结果以酶切寡聚透明质酸钠为基质材料制备ARM可溶解微针,抗湿性优良。压力大于30 N(0.178 N/针)时,可将微针阵列刺入猪皮。微针刺入猪皮后渗透速率在6~8 h达到最高,8 h后逐渐下降。大鼠体内药代动力学试验表明,ARM可溶解微针贴片透皮给药与肌内注射相比,生物利用度相近,但前者血药浓度更平稳。结论 ARM可溶解微针透皮贴片是一种生物利用度高,具有缓释效果的抗疟新剂型。OBJECTIVE Artemether （ARM） is an artemisinin derivative with strong anti-malaria activity. However, it is poorly soluble in water,leading to low oral bioavailability. And the fast d~＇ug metabolism leads to effective plasma concentration maintaining for a short time. The aim of the study was to develop dissolving microneedles loaded with artemetber （ARM） , to overcome the shortcomings of existing ARM preparations. METHODS A novel preparation method of ARM-loaded dissolving microneedles （DMNs） was established. Hygroscopic property, mechanical strength, stability, and the in vitro^in vivo drug release property of the prepared ARM- loaded DMNs were characterized. RESULTS It indicated excellent humidity resistance of the enzyme oligomeric sodium hyaluronate （Oligo-HA） based DMNs. The percentage of microconduits created in the skin at insertion forces of 30 N （0. 178 N/needle） were approximately 100%. The maximum penetration rate of ARM delivered by DMNs was obtained during 6-8 h. After that,the penetration rate was gradually decreased. The pharmacokinetics study in rats showed that in contrast to intramuscular injection, more stable plasma ARM and similar bioavailability was obtained by DMNs application. CONCLUSION Developed DMNs provided a potential minimally invasive route for ARM with high bioavailability and sustained-release effect.

关 键 词：蒿甲醚 微针 透明质酸钠 透皮给药 

分 类 号：R943[医药卫生—药剂学]