We first demonstrate a simple and rapid fabrication protocol of bovine serum albumin (BSA) nanoparticles (NPs), as potential drug carriers using a microchannel flow technique with the successful encapsulation of a water-soluble kynurenic acid (KYNA) having neuroactive property has also been performed. By comparison, the preparation of a hydrophobic α-Tocopherol (TP)-loaded polylactide-co-glycolide 50:50 (PLGA50)-based NPs was also carried out under flow conditions. We highlight several benefits of the flow technique over the commonly known self-assembly and nanoprecipitation processes. The average particle diameter, the size distribution, the encapsulation efficiency (EE%) and the drug release kinetics of these different core-shell type NPs prepared by the flow as well as the above-mentioned classic methods were compared. The decisive role of the flow rate (FR), the relative flow rate (RFR) of the components in the particle size of both BSA-and PLGA50-based NPs have also been verified. By utilization of the optimal flow conditions, the average size can be decreased with ca. 15-20% and lower polydispersity index (PDI) can be also achieved. It was confirmed that the systematic change of the RFR values resulting in the controlled size of the drug-loaded BSA NPs between 120 and 140 nm, while d = 149 nm was obtained for self-assembled NPs. However, for BSA-based NPs quite similar EE% was obtained for both methods (ca. 11-12%), but for PLGA50/TP NPs the application of flow device increased the EE% from 67.0% to 71.5%.