单一或复合高分子材料用于载药可溶性聚合物微针的制备

doi:10.11896/cldb.18040131

材料导报

2019, Vol. 33

Issue (10): 1738-1744 https://doi.org/10.11896/cldb.18040131

高分子与聚合物基复合材料

单一或复合高分子材料用于载药可溶性聚合物微针的制备

占浩慧, 黄颖聪, 马凤森

浙江工业大学药学院,生物制剂与材料实验室,杭州 310014

Drug-loaded Dissolving Microneedles Prepared by Single or Composite Polymer Materials

ZHAN Haohui, HUANG Yingcong, MA Fengsen

Biologics and Biomaterials Laboratory, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014

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摘要微针是一种新型的经皮药物递送技术,近年来可溶性微针作为其中的一类引起了研究者极大的关注。本研究通过文献及实验筛选优化可溶性聚合物微针的最适制备工艺;选择透明质酸(HA)、硫酸软骨素(CS)、聚乙烯吡咯烷酮(PVP)、聚乙烯醇(PVA)、羧甲基纤维素(CMC)、甲基乙烯基醚-马来酸酐共聚物(Gantrez)和羟丙基甲基纤维素(HPMC)这几种常见的高分子材料,分别以单一或复合的方式将高分子材料制备为载有模型药物盐酸利多卡因的可溶性聚合物微针。微针阴模模具通过金属微针倒模制得,可溶性微针通过阴模浇注制得。根据材料和药物的溶解性,以针型和气泡现象作为评判指标筛选出去离子水作为合适的微针制备溶剂。微针基质溶液中的气泡可以通过离心法快速、有效地去除。以外观形态、力学性能及吸湿性为评价指标,研究各个聚合物材料制备载药可溶性聚合物微针的可行性。调整优化处方中各个组分间的比例,以筛选出力学性能优良、不易吸湿且载有大剂量药物的聚合物材料;并对最优处方制备的可溶性微针进行表征及力学性能评价。结果表明,以Gantrez S-97和HPMC这两种高分子材料复合制备的微针能载有70%的盐酸利多卡因,可顺利穿刺皮肤,力学性能优良且不易吸潮,可实现大剂量药物的顺利递送。

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	占浩慧
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关键词: 可溶性微针盐酸利多卡因高分子材料力学性能高载药量

Abstract: Microneedles is a novel type of transdermal drug delivery technology based on macromolecule polymers. The research of dissolving microneedles has aroused enormous attention, recently. The optimum preparation conditions of dissolving microneedles were optimized through lite-rature review and experiments. Several common polymer materials including hyaluronic acid (HA), chondroitin sulfate (CS), polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), poly(methylvinylether-co-maleic anhydride) (Gantrez) and hydroxypropyl methyl cellulose (HPMC) were selected to synthesize the dissolving microneedles in a single or composite manner, in which model drug lidocaine hydrochloride was loaded. Specifically, the female mold was made from metal microneedles by reverse mould method, and the dissolving microneedles were prepared by casting method. According to the solubility of the polymer materials and the model drug, the suitable solvent for preparing microneedles was screened out. Dissolving microneedles prepared with distilled water presented favorable needle shape and less bubbles. Bubbles in matrix solution could be eliminated by centrifugation in a fast and efficient way. Taking the morphology, mechanical pro-perty and hygroscopicity as the evaluation indicators, the feasibility of preparing drug-loaded dissolving microneedles from various polymer materials was studied. The proportions of the various components were adjusted and optimized to find out the polymer materials with excellent mechanical properties, moisture resistance and high drug loading amount. Dissolving microneedles prepared by optimal parameters were characterized by SEM and skin puncture experiment. The results indicated that the microneedles prepared by macromolecule polymers of Gantrez S-97 and HPMC at a mass ratio of 4∶1 were able to load with 70wt% lidocaine hydrochloride. It possessed excellent mechanical properties and slight hygroscopicity, which could easily penetrate into the skin and realize the smooth delivery of large dosage of drugs.

Key words: dissolving microneedles lidocaine hydrochloride polymer materials mechanical properties high drug loading

发布日期: 2019-05-16

ZTFLH:

R944.9

基金资助: 浙江省重点科技创新团队项目 (2013TD15)

通讯作者: merrigen@126.com

作者简介: 占浩慧,2016年6月毕业于武汉工程大学药物制剂专业,获得理学学士学位。现为浙江工业大学药学院硕士研究生,在马凤森教授的指导下进行研究。目前主要研究领域为基于可溶性聚合物微针的生物活性分子经皮递送。马凤森,浙江工业大学教授,硕士研究生导师。作为浙江省药学界的资深专家,担任浙江省药学会生物制药和医疗器械两个专业委员会的主要负责人。带领的实验室多年来专业从事经皮新型药物制剂、生物药物和生物材料等的研究开发工作,积累了相关研究工作与团队、共性关键技术、系列产品应用等方面的基础,尤其是近些年来对微针阵列技术的系统深入研究。业已申请/获得多项国家发明专利,发表了多篇论文。

引用本文:

占浩慧, 黄颖聪, 马凤森. 单一或复合高分子材料用于载药可溶性聚合物微针的制备[J]. 材料导报, 2019, 33(10): 1738-1744.
ZHAN Haohui, HUANG Yingcong, MA Fengsen. Drug-loaded Dissolving Microneedles Prepared by Single or Composite Polymer Materials. Materials Reports, 2019, 33(10): 1738-1744.

链接本文:

http://www.mater-rep.com/CN/10.11896/cldb.18040131 或 http://www.mater-rep.com/CN/Y2019/V33/I10/1738

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