Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and Pluronic^® F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemico–physical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %Pluronic^® F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized.

中文翻译：

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用于生产混合纳米药物的微流体技术

微流体技术最近被用作生产各种纳米药物 (NMeds) 的创新方法，在全球范围内展示了它们的潜力。精确控制变量（例如流速比、温度、总流速等）的能力允许 NMed 系统具有更大的可调性，这些系统比通过众所周知的台式协议获得的系统更加标准化和自动化。然而，能够获得与先前优化的 NMeds 具有相同特征的 NMeds 是一个关键方面。在这项研究中，我们集中在生产协议用于混合NMed​​s（H-NMeds）选自PLGA，胆固醇，和Pluronic的转移^®F68 从台式纳米沉淀法到微流体装置。为此，我们修改了参数，例如流速比、有机相中核心材料的浓度以及进料有机相中 PLGA 与胆固醇的比率。分析的输出是化学物理特性，例如尺寸、PDI 和表面电荷，以胆固醇百分比和残留百分比 Pluronic ^{® 表示的组成}F68，它们对冻干的稳定性，以及通过原子力和电子显微镜观察的形态。根据结果​​，即使微流控技术是获得 NMeds 工业生产的独特程序之一，我们证明了从台式方法到微流控方法的转换不是简单地转移已经建立的参数，有几个变量需要考虑和优化。