Microfluidic manufacturing improves polydispersity of multicomponent polymeric nanoparticles

A key challenge in manufacturing of multicomponent polymeric colloids is obtaining monodisperse nanoparticles (NPs) with reproducible characteristics. Herein, NP formulations with varying core to shell ratios were either prepared by bulk nanoprecipitation or microfluidic synthesis and evaluated regarding their size and polydispersity. Microfluidic process parameters, such as the total flow rate (TFR) and the flow rate ratio (FRR) of the aqueous phase and the organic polymer solution, were varied to tune particle size and further improve size distribution. In general, bulk nanoprecipitation resulted in formation of larger particles (52-65 nm) with a wide size distribution, whereas particles were significantly smaller in size (24-43 nm) and displayed a rather monodisperse size distribution when they were manufactured with a microfluidic system. The FRR was identified to be the key factor for improving the size distribution of NPs with a high ratio of PLA-PEG to PLGA, whereas it had only minor impact on particle characteristics of formulations with a lower copolymer ratio. Polydispersity of different NP formulations was successfully improved by microfluidic manufacturing, demonstrating that this technology is a valuable tool that allows for reproducible and scalable manufacturing of multicomponent NPs with precisely tunable quality attributes.