Microfluidic Synthesis of PLA Nanoparticles: Comparison of Different Systems to Achieve High Scalability and Batch-to-batch Reproducibility

In recent years, plastic materials labelled as “environmentally sustainable” have emerged, primarily composed of biodegradable polymers such as polylactic acid (PLA). Originally developed for pharmaceutical applications, these biopolymers are bioresorbable while maintaining mechanical characteristics comparable to conventional, non-biodegradable plastics. However, the increasing prevalence of bioplastic-based products warrants a cautious evaluation, as their accelerated degradation may lead to a faster and potentially problematic accumulation of micro- and nanoparticles in living tissues.1 For this reason, the production of PLA-based nanoparticles (NPs) is of great relevance for both in vitro and in vivo studies, aiming to investigate the potential biological effects of micro- and nanoplastics on living cells and tissues. Moreover, ensuring the ability to produce these nanoparticles on a large scale is essential to conduct in vivo experiments on statistically significant populations of animal models, thereby increasing the reliability and translational relevance of the findings. This study investigates the synthesis of PLA nanoparticles using various microfluidic systems, focusing on scalability and batch-to-batch reproducibility, two critical parameters for translational nanomedicine. Comparative analysis is conducted on single-phase flow, droplet-based, and staggered herringbone micromixers (SHMs). PLA nanoparticles are synthesized via nanoprecipitation and characterized in terms of size, polydispersity index (PDI), and encapsulation efficiency. The results highlight the trade-offs between throughput, precision, and system complexity, offering insights into the most viable platforms for industrial-scale nanoparticle production.