Abstract
Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this technology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type ofmicroparticles with gelatinmethacrylate (GelMa) cores and poly(L-lactide-co-glycolide) (PLGA) shells for synergistic and sustained drug delivery applications. The microparticles were fabricated by using GelMa aqueous solution and PLGA oil solution as the raw materials of the microfluidic 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 polymerized 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 microparticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by manipulating the flow solutions during the microfluidic emulsification. Because of the solid structure of the resultant microparticles, 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 microparticlesmake them ideal for drug delivery applications.
摘要
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.
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Acknowledgments
This work was 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, and the Scientific Research Foundation of Southeast University. D Yan also thanks the Foundation of Jiangsu Cancer Hospital (ZN201609) and Beijing Medical Award Foundation (YJHYXKYJJ-433).
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The first two authors contributed equally to this work.
Author contributions Zhao Y conceived the idea and designed the experiments; Li Y, YanDand Fu F carried out the experiments; Zhao Y and Li Y analyzed the data and wrote the manuscript; Liu Y, Zhang B,Wang J, Shang L and Gu Z contributed to scientific discussion of the article.
Conflict of interest The authors declare that they have no conflict of interest.
Supplementary information Supporting data are available in the online version of the paper.
Yanna Li is currently a graduate student at the School of Biomedical Engineering, Southeast University. She joined Prof. Yuanjin Zhao’s research group in 2013. Her current research focuses on the fabrication of microparticles by using droplet microfluidics.
Dan Yan is currently an associate chief physician at the Department of Pharmacy, Jiangsu Cancer Hospital. She received her PhD degree in 2011 from China Pharmaceutical University. Her current research focuses on the clinical drug delivery.
Yuanjin Zhao received his PhD degree in 2011 from Southeast University. In 2009–2010, he worked as a research scholar in Prof. David A. Weitz’s group at the School of Engineering & Applied Sciences, Harvard University. Since 2015, he has been a full professor of Southeast University. His current scientific interests include microfluidic-based materials fabrication, biosensors, and bio-inspired photonic nanomaterials.
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Li, Y., Yan, D., Fu, F. et al. Composite core-shell microparticles from microfluidics for synergistic drug delivery. Sci. China Mater. 60, 543–553 (2017). https://doi.org/10.1007/s40843-016-5151-6
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DOI: https://doi.org/10.1007/s40843-016-5151-6