Tuning the size of poly(butylene oxide) nanoparticles by microfluidic-assisted nanoprecipitation

• First microfluidic nanoprecipitation of polybutylene oxide nanoparticles • Ψ-geometry channels yield smaller, more uniform nanoparticles than T-geometries • Low flow rate ratios promote rapid mixing and enhance nanoparticle uniformity • High total flow rates improve mixing while maintaining laminar flow conditions • Miniaturized channels (20 µm) improve size control via enhanced diffusion Microfluidic-assisted nanoprecipitation provides precise control over formulation conditions, enabling for the design of nanoparticles with highly tunable properties. This study explores the influence of channel geometry, flow dynamics, and polymer concentration on the size and polydispersity of poly(butylene oxide) (PBO) nanoparticles. PBO is a hydrophobic polymer with a low glass transition temperature ( T g = –71 °C) that typically forms large nanoparticles (>176 nm) via bulk nanoprecipitation, as well as aggregates ranging from 3000–5000 nm. Using a hydrodynamic flow-focusing Ψ-geometry, we demonstrate that higher total flow rates increase convective mixing, reduce mixing times, and produce smaller, more monodisperse PBO nanoparticles. A comparative analysis of Ψ- and T-channel geometries across various dimensions revealed that Ψ-geometries consistently outperformed T-geometries due to their superior mixing efficiency. Decreasing the channel dimensions to 20 µm further improved mixing by shortening diffusion lengths and accelerating solvent–antisolvent interdiffusion. Using the Ψ-geometry, nanoparticles as small as 66 nm were achieved, whereas T-geometries produced significantly larger particles (>500 nm). A linear trend between particle size and total flow was observed, best described by a power-law relationship, linking flow rate—and by extension, Reynolds number—to mixing speed and nanoparticle size. These findings highlight the pivotal role of microfluidic design and flow control in tailoring nanoprecipitation for low- T g , hydrophobic polymers such as PBO. This approach shows promising potential for the encapsulation and delivery of hydrophobic drugs.