Lyophilizable Polymer–Lipid\nHybrid Nanoparticles\nwith High Paclitaxel Loading

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