Lyophilizable Polymer–Lipid Hybrid Nanoparticles with High Paclitaxel Loading

Lyophilization is a prevalent technique for preparing paclitaxel (PTX) clinical formulations. However, the instability of PTX nanoparticles poses challenges in producing lyophilized formulations. Such an instability involves maintaining stable dispersions and structural integrity during lyophilization. To tackle these issues, flash nanoprecipitation method is employed to prepare highly stable and loaded lyophilizable diPTX-SS nanoparticles, achieving over a month of nanosuspension stability and 91 wt % loading capacity. Furthermore, adjusting the concentrations and stabilizer ratios allows for controlled nanoparticle preparation with surface structures suitable for lyophilization. The hybridization of PLGA-PEG and DSPE-PEG increases the surface PEG layer content, creating a corona-like outer layer that maintains nanoparticle integrity during lyophilization, and ensures excellent redispersibility for postlyophilization without excessive cryoprotectants. Additionally, responsive release behavior, along with in vitro and in vivo experiments, confirms that these lyophilizable hybrid diPTX-SS nanoparticles effectively suppress tumor growth and vascular endothelial proliferation, offering insights for clinical PTX formulation development.