Composite core-shell microparticles from microfluidics for synergistic drug delivery  

基于乳液微流控技术的核壳结构复合微胶囊药物载体开发研究（英文）

作　　者：李艳娜 燕丹 付繁繁 刘羽霄 张彬 王洁 商珞然 顾忠泽 赵远锦 

机构地区：[1]State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nan)ing 210096, China [2]Department of Pharmacy, Jiangsu Cancer Hospital, Nanjing 210009, China

出　　处：《Science China Materials》2017年第6期543-553,共11页中国科学（材料科学（英文版）

基　　金：supported by the National Natural Science Foundation of China (21473029 and 51522302) ;the NSAF Foundation of China (U1530260);the National Science Foundation of Jiangsu (BK20140028) ;the Program for New Century Excellent Talents in University;the Scientific Research Foundation of Southeast University;Foundation of Jiangsu Cancer Hospital (ZN201609);Beijing Medical Award Foundation (YJHYXKYJJ-433)

摘　　要：Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this tech- nology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate （GelMa） cores and poly（L-lactide-co-glycolide） （PLGA） shells for syn- ergistic and sustained drug delivery applications. The mi- croparticles were fabricated by using GelMa aqueous solu- tion and PLGA oil solution as the raw materials of the mi- croflnidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride （DOX, hydrophilic） and camptothecine （CPT, hydrophobic）, could be loaded respectively. As the inner cores were poly- merized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the micropar- ticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by ma- nipulating the flow solutions during the microfluidic emulsi- fication. Because of the solid structure of the resultant mi- croparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.微胶囊在药物递送系统中具有重要的应用价值.目前关于该领域的研究主要集中于开发新型微胶囊来提高药物递送系统的效率.本文提出了一种可协同运输和缓慢释放药物的微胶囊,其由明胶甲基丙烯酸接枝共聚物(GelMa)内核和聚乳酸羟基乙酸共聚物(PLGA)外壳组成.在微胶囊的制备过程中,使用液滴微流控技术,将溶有盐酸阿霉素(DOX)的GelMa水溶液和溶有喜树碱(CPT)的PLGA油溶液乳化成均匀的双乳液模板,通过紫外固化模板内核,通过溶剂挥发固化模板壳层.该过程避免了乳液的破损及包裹液的流出,因此可显著提高药物的包裹效率.通过调节微流控的流速,还可精确地调节微粒的尺寸和结构.由于所制备的微胶囊内核和外壳都为固化状态,其包裹的活性药物只能随着载体材料的降解而缓慢释放出来,这就避免了其他种类药物载体所面临的药物突释现象.本研究所开发的微胶囊的这些优良特性使其成为药物递送系统中的理想选择.

关 键 词：microfluidic EMULSION micropartide drug delivery biomaterial 

分 类 号：TQ460.6[化学工程—制药化工]