An effective delivery vehicle of genetic materials to their target site is the key to a successful gene therapy. In many cases, nanoparticles are used as the vehicle of choice and the efficiency of the delivery relies heavily on the physicochemical properties of the nanoparticles. Microfluidics, although being a low throughput method, has been increasingly researched for the preparation of nanoparticles. A range of superior properties were claimed in the literature for microfluidic-prepared platforms, but no evidence on direct comparison of the properties of the nanoparticles prepared by microfluidics and conventional high throughput method exists, leaving the industry with little guidance on how to select effective large-scale nanoparticle manufacturing method. This study used plasmid DNA-loaded PLGA-Eudragit nanoparticles as the model system to critically compare the nanoparticles prepared by conventional and microfluidics-assisted nanoprecipitation. The PLGA-Eudragit nanoparticles prepared by microfluidics were found to be statistically significantly larger than the ones prepared by conventional nanoprecipitation. PLGA-Eudragit nanoparticle prepared conventionally showed higher DNA loading efficiency. Although the DNA-loaded nanoparticles prepared by both methods did not induce significant cytotoxicity, the transfection efficiency was found to be higher for the ones prepared conventionally which has good potential for plasmid delivery. This study for the first time provides a direct comparison of the DNA-loaded nanoparticles prepared by microfluidic and conventional methods. The findings bring new insights into critical evaluation of the selection of manufacturing methods of nanoparticles for future gene therapy.

将遗传材料有效传递到其靶位点是基因治疗成功的关键。在许多情况下，纳米粒子被用作选择的载体，递送效率在很大程度上取决于纳米粒子的物理化学特性。微流体虽然是一种低通量方法，但已越来越多地研究用于制备纳米颗粒。文献中声称微流体制备的平台具有一系列优异的性能，但没有证据表明微流体制备的纳米粒子的性质与传统的高通量方法存在直接比较，这使得业界几乎没有关于如何选择有效的大分子的指导。级纳米粒子制造方法。本研究使用载有质粒 DNA 的 PLGA-Eudragit 纳米颗粒作为模型系统，对通过传统和微流体辅助纳米沉淀制备的纳米颗粒进行严格比较。发现通过微流体制备的 PLGA-Eudragit 纳米颗粒在统计学上显着大于通过常规纳米沉淀制备的纳米颗粒。常规制备的 PLGA-Eudragit 纳米颗粒显示出更高的 DNA 加载效率。尽管通过这两种方法制备的载有 DNA 的纳米粒子没有引起显着的细胞毒性，但发现传统制备的纳米粒子的转染效率更高，具有良好的质粒传递潜力。这项研究首次直接比较了通过微流体和传统方法制备的载有 DNA 的纳米粒子。