Page 70 - 2020年17期

马钱子碱双层聚合物可溶性微针的制备及其在不同载药方式下

的体外经皮渗透性研究 Δ

汪云霞 ，宋信莉 ，陈欢欢 ，陈振龙 ，刘 文（1.贵州中医药大学药学院，贵阳 550025；2.贵州医科大学附属
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医院党办，贵阳 550004）
中图分类号 R283.6 文献标志码 A 文章编号 1001-0408（2020）17-2112-07
DOI 10.6039/j.issn.1001-0408.2020.17.12

摘 要 目的：制备马钱子碱（Bru）双层聚合物可溶性微针，并考察其在不同载药方式下的体外经皮渗透特性。方法：以微针揭膜
难易程度、阵列完整性、气泡量、针型、针尖硬度、背衬韧性等为考察指标分别筛选微针的针尖材料和背衬材料，并以微针形态为考
察指标筛选基质溶胀方法和干燥方法，然后采用两步法制备双层聚合物可溶性微针，并进行表征和安全性评价。通过Franz扩散
池法考察针尖载药、背衬载药、全载药Bru双层聚合物可溶性微针的体外经皮渗透特性，绘制体外透皮曲线并计算累积渗透量（Q）
和累积渗透率。结果：优选的双层聚合物可溶性微针的制备工艺为以硫酸软骨素-聚乙烯吡咯烷酮K30（1∶1，m/m）作为针尖材料，
15％聚乙烯醇作为背衬材料，在4 ℃冰箱静置1 h进行基质溶胀，干燥器室温干燥24 h。所制微针阵列完整，机械性能良好，能成
功刺穿铝箔和大鼠皮肤，微针处理后皮肤在6 h内即可恢复到原来的状态。体外透皮试验结果显示，微针递药可大大提高Bru的
经皮累积渗透量，针尖材料可在10 min内溶解并释放药物；针尖载药微针在8 h 内基本释放完全，Q8 h为102.185 μg/cm ，累积渗透
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率达到 94.05％；背衬载药、全载药微针在 8 h 内的药物累积渗透率均超过 50％，48 h 药物累积渗透率均超过 90％，Q48 h分别为
840.77、1 156.73 μg/cm ，显示出缓释特性。结论：成功制备了针尖层硬、背衬层软的Bru双层聚合物可溶性微针，通过全载药的方
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式可实现药物的有效经皮递送并达到缓释效果。
关键词 马钱子碱；双层聚合物；可溶性微针；制备工艺；经皮递药
Study on the Preparation of Brucine Bilayer Polymer Soluble Microneedle and Its in vitro Transdermal
Permeability under Different Drug Loading Modes
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WANG Yunxia ，SONG Xinli ，CHEN Huanhuan ，CHEN Zhenlong ，LIU Wen（1. School of Pharmacy，Guizhou
University of TCM，Guiyang 550025，China；2. Party Office，the Affiliated Hospital of Guizhou Medical
University，Guiyang 550004，China）
ABSTRACT OBJECTIVE：To prepare Brucine（shorted for“Bru”）bilayer polymer soluble microneedles，and to investigate
their in vitro transdermal permeation characteristics under different drug loading modes. METHODS：Taking the degree of difficulty
of microneedle film uncovering，array integrity，bubble amount，needle shape，tip hardness and backing toughness as the indexes，
tip and backing materials were screened. The swelling method and drying method of matrix were screened using the morphology of
microneedles as index. The double-layer polymer soluble microneedle was prepared by two-step method，then it was characterized
and evaluated in the safety. The in vitro transdermal permeation characteristics of tip-loaded，backing-loaded and full-loaded Bru
bilayer polymer soluble microneedles were investigated by Franz diffusion cell. The in vitro skin penetration curve was drawn，and
the cumulative permeability amount （Q） and cumulative permeability rate were calculated. RESULTS：The optimal preparation
technology of bilayer polymer soluble microneedles included chondroitin sulfate（CS）and polyvinylpyrrolidone K30（PVP K30）
（1 ∶ 1，m/m）as tip materials，15％ polyvinyl alcohol（PVA）as backing material，matrix swelling in the refrigerator at 4 ℃ for 1
h，and drying at room temperature for 24 h in dryer. Prepared microneedle array was complete and had good mechanical
properties，and could successfully puncture aluminum foil and
Δ 基金项目：贵州省科技厅 2017 年度学术新苗培养及创新探索 rat skin. After microneedle treatment，the skin could return to
专项项目（No.黔科合平台人才〔2017〕5735号-26）；贵州省教育厅普通 its original state within 6 h. The results of in vitro transdermal
高等学校科技拔尖人才支持计划（No.黔教合 KY 字〔2017〕074）；贵州
test showed that microneedle drug delivery could greatly
省一流专业（中药学）建设项目子课题（No.黔高教发〔2017〕158
increase the cumulative transdermal permeability amount of
号-02-32 号）；贵州省国内一流建设学科项目（中药学）（No.GNYL
Bru，and the tip material could dissolve and release the drug
〔2017〕008号）；国家中医药管理局邱德文全国名老中医药专家传承工
within 10 min； the tip-loaded microneedle was basically
作室建设项目
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＊硕士研究生。研究方向：中药新技术与新制剂。E-mail： released within 8 h，Q 8 h was 102.185 μg/cm and the cumulative
317081060@qq.com permeability rate reached 94.05％ ； the drug cumulative
# 通信作者：副教授，硕士生导师，硕士。研究方向：中药新技术 permeability rate of backing-loaded and full-loaded microneedles
与新制剂。E-mail：392347047@qq.com exceeded 50％ within 8 h and exceeded 90％ within 48 h；Q 48 h

·2112 · China Pharmacy 2020 Vol. 31 No. 17 中国药房 2020年第31卷第17期