In recent years, microfluidic devices present unique advantages for the development of a new generation of nanoparticle synthesis method compared to bulk methods. In this study, we report a microfluidic flow-focusing method for the production of all trans retinoic acid (ATRA)-loaded methoxy poly(ethylene glycol)-poly(lactide-coglycolide) (mPEG-PLGA) nanoparticles (NPs). Box–Behnken experimental design (BBD) was applied to optimize of formulation ingredients and process conditions with minimum particle size, maximum drug loading% (DL%) and encapsulation efficiency% (EE%). Polymer concentration, drug concentration and flow rates of solvent (S) and antisolvent (AS) were selected as independent variables. Based on optimization strategy, minimum particle size achieved shows average (SD) particle size of [Formula: see text][Formula: see text]nm with DL of [Formula: see text][Formula: see text]wt.% and EE of [Formula: see text][Formula: see text]wt.%, respectively. While maximum DL has been reported to be [Formula: see text][Formula: see text]wt.% with particle size of [Formula: see text][Formula: see text]nm and EE of [Formula: see text][Formula: see text]wt.%, respectively. Moreover, the results have shown that the AS/S ratio represents the most significant effect on particle size. Indeed, increasing the AS flow rate directly results in generating smaller particles. The AS/S ratio represents the least significant effect on DL%, such that, at fixed flow rates, higher DL was observed at high concentration of drug and lower concentration of polymer. In conclusion, optimization of the ATRA-loaded mPEG-PLGA NPs by BBD yielded in a favorable drug carrier for ATRA that could provide a new treatment modality for different malignancies.

中文翻译：

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使用微流体流动聚焦装置制备全反式维甲酸负载 mPEG-PLGA 纳米粒子以控制药物输送

近年来，与本体方法相比，微流控装置在新一代纳米粒子合成方法的开发方面呈现出独特的优势。在这项研究中，我们报告了一种用于生产所有反式维甲酸 (ATRA) 负载的甲氧基聚 (乙二醇)-聚 (丙交酯-共乙交酯) (mPEG-PLGA) 纳米粒子 (NPs) 的微流体流动聚焦方法。Box-Behnken 实验设计 (BBD) 用于优化配方成分和工艺条件，具有最小粒径、最大载药量% (DL%) 和封装效率% (EE%)。选择聚合物浓度、药物浓度和溶剂（S）和抗溶剂（AS）的流速作为自变量。基于优化策略，达到的最小粒径显示[公式：见正文][公式：见文字]nm，DL为[公式：见文字][公式：见文字]wt.%和EE为[公式：见文字][公式：见文字]wt.%。虽然据报道最大 DL 为 [公式：见正文][公式：见正文]wt.%，粒径为 [公式：见正文][公式：见正文]nm，EE 为 [公式：见正文][公式：分别见正文]wt.%。此外，结果表明，AS/S 比对粒度的影响最为显着。事实上，增加 AS 流速直接导致产生更小的颗粒。AS/S 比对 DL% 的影响最不显着，因此，在固定流速下，在药物浓度高和聚合物浓度低时观察到更高的 DL。综上所述，