Bioinspired Leaf-Vein Micromixer for a Rapid and Efficient Synthesis of Monodisperse Ciprofloxacin Lipid Nanoparticles

Inspired by plant vascular architectures and leveraging hierarchical vein-branching principles, this study pioneers a biomimetic leaf-venation groove micromixer (LVGM) to address critical limitations in passive microfluidic mixing and conventional liposome preparation. Through systematic numerical simulations, we elucidate the flow field characteristics and vortex-driven mixing mechanisms of the LVGM architecture, complemented by experimental validation of its mixing performance and nanocarrier synthesis capabilities. The bioinspired groove configuration induces hierarchical vortical flows that amplify chaotic advection, achieving exceptional mixing efficiencies (>99%) across broad Reynolds numbers (Re = 0.1–100). When applied to the nanopharmaceutical synthesis, the LVGM enables single-step fabrication of ciprofloxacin-loaded liposomes (CIP-LNPs) with precise size control (131.8 ± 1.84 nm) and narrow dispersity (polydispersity index (PDI) = 0.213 ± 0.009). The engineered nanoparticles demonstrate remarkable colloidal stability (<6.97% size variation over 14 days at 4 °C), with surface characteristics and morphological uniformity confirmed through zeta potential analysis (−34.7 ± 0.86 mV) and transmission electron microscopy (TEM) imaging. Cytotoxicity evaluation revealed that CIP-LNPs maintained >80% viability of L929 fibroblasts at concentrations ≤20 μg·mL–1, confirming their excellent biocompatibility. This vascular-mimetic microfluidic platform advances drug delivery technology by combining energy-efficient operation with scalable manufacturing potential while establishing new paradigms for bioinspired microsystems in precision nanomedicine applications.