Microfluidic mixing system for precise PLGA-PEG nanoparticles size control

In this study, a microfluidic device was employed to produce polymeric nanoparticles (NPs) with well-controlled sizes. The influence of several parameters in the synthesis process, namely, polymer concentration, flow rate and flow rate ratio between the aqueous and organic solutions was investigated. To evaluate the NPs size effect, three diameters were selected (30, 50 and 70 nm). Their cytocompatibility was demonstrated on endothelial cells and macrophages. Additionally, their efficacy to act as drug carriers was assessed in an in vitro inflammatory scenario. NPs loaded and released diclofenac (DCF) in a size-dependent profile (smaller sizes presented lower DCF content and higher release rate). Moreover, 30 nm NPs were the most effective in reducing prostaglandin E2 concentration. Therefore, this study demonstrates that microfluidics can generate stable NPs with controlled sizes, high monodispersity and enhanced batch-to-batch reproducibility. Indeed, NPs size is a crucial parameter for drug encapsulation, release and overall biological efficacy.The authors would like to thank funding that allowed to carry out this work namely, the Fundacao para a Ciencia e a Tecnologia (FCT) for the S. Gimondi (PD/BD/143140/2019), C. F. Guimaraes (PD/BD135253/2017) and S. F. Vieira (PD/BD/135246/2017) fellowships. This work was also supported by FROnTHERA (NORTE-01-0145-FEDER-000023), Cells4_IDs (PTDC/BTM-SAL/28882/2017) and the NORTE 2020 Structured Project, co-funded by Norte2020 (NORTE-01-0145-FEDER-000021). We also thank Dr. Isabel Leonor for the precious support for the SEM microscopy and AFM images