Microfluidic synthesis of PLGA nanoparticles enabled by an ultrasonic microreactor†

We present an ultrasonic microreactor for synthesising poly(lactic-co-glycolic) acid (PLGA) nanoparticles through the emulsion-solvent evaporation technique. Monodispersed PLGA nanoparticles (polydispersity index (PDI) < 0.3) in the size range of 20–300 nm are desired for biomedical applications. An ultrasonic microreactor with rough microchannels is utilised for the synthesis of PLGA nanoparticles. Through a comprehensive parametric investigation, we identify the optimal ultrasonic power, PLGA concentration, and aqueous-to-organic phase flow rate ratio, to minimise the size of the PLGA nanoparticles. By varying the operational parameters and the concentration of PLGA, the mean hydrodynamic diameter of the monodispersed PLGA nanoparticles (PDI of 0.1–0.2) can be varied within the range of 115–150 nm. Furthermore, the successful encapsulation of a hydrophobic dye, Nile Red, is demonstrated, where a dye loading (DL) of up to 0.34% is achieved, which is in agreement with the previously reported loading of Nile Red. The in vitro release study performed for the Nile Red-loaded PLGA nanoparticles (NR-PLGA) reveals a triphasic release profile of Nile Red. In summary, this work highlights the potential of the ultrasonic microreactor as a versatile platform for the synthesis of PLGA nanoparticles suitable for biomedical applications.