基于液滴微流控技术的药物研发及研究进展

Drug Development Based on Droplet Microfluidics and Its Research Progress

摘要:

单分散性载药缓释微球作为新型药物释放系统,已成为缓释药物制剂研究的热点之一。传统制备方法获得的载药微球大多存在大小不均一、粒径分布宽、载药量低、缓释效果不明显等问题,极大地限制了其应用。液滴微流控技术是一种通过芯片微通道结构，实现在微尺度上对流体进行精细操控，形成高通量的结构和微液滴尺寸精确可调的新型制备工艺。微流控芯片作为微液滴技术的载体，可采用多种材料及制备工艺制备，以适用于不同种类的溶剂，进一步拓展其应用范围。通过微流控技术生产出的液滴具有体积小、尺寸均匀、封闭环境和内部稳定等特点，并能形成特定结构与功能的微球，在纳米材料、制药工程和生命科学等相关领域中具有巨大的应用潜力。相对于传统的微球制备方法，液滴微流控技术不仅可以构建多种形态的微球，还能提供优秀的模板，丰富和扩展微球的应用领域。以科学原理及应用实例为综述主线，概括了微液滴生成的机理及流道设计（包括T型通道法、流动聚焦法和共轴流法等），对不同结构形貌与特定功能的微球进行了归纳梳理（实心微球、Janus颗粒、核壳结构、多孔结构和不规则结构等），重点介绍了其在药物研发中的应用。通过对微液滴技术的研究现状的概括总结，提出了未来研究的方向及建设性意见。

Abstract:

Monodisperse drug-loaded sustained-release microspheres， as an innovative drug release system， have become a focal point in the research of sustained-release pharmaceutical formulations. However， the traditional preparation methods often result in microspheres with uneven sizes， broad particle size distributions， low drug loading capacities， and unclear sustained-release effects， significantly limiting their applications. Droplet microfluidics is an advanced fabrication technique that utilizes microchannel structures on chips to precisely control fluids at the microscale， enabling high-throughput production of microdroplets with tunable sizes and structures. Serving as carriers for microdroplet technology， microfluidic chips can be made from various materials and through different fabrication processes to accommodate diverse solvents， thus broadening their applications. Microdroplets produced via microfluidic technology are characterized by their small volume， uniform size， enclosed environment， and internal stability， and can form microspheres with specific structures and functions. This has great potential in fields such as nanomaterials， pharmaceutical engineering， and life sciences. Compared to traditional microsphere preparation methods， droplet microfluidics not only facilitates the creation of microspheres in various shapes but also provides excellent templates that enhance and diversify the applications of microspheres. This paper reviews the scientific principles and application examples of microdroplet generation， including the mechanisms of microdroplet formation and channel design （such as T-junction， flow focusing， and coaxial flow methods）. It also categorizes microspheres with different structural morphologies and specific functions （solid microspheres， Janus particles， core-shell structures， porous structures， and irregular structures） and highlights their applications in drug development. The current status and progress of microdroplet technology research are outlined， and constructive suggestions and future research directions are proposed.