Design and Assessment of PLGA based Tetrandrine Nanoparticles for Intranasal delivery targeting for Glioblastoma

Glioblastoma multiforme represents a malignant brain tumor characterized by poor treatmentavailability. This study aimed to enhance nasal-to-brain delivery of tetrandrine, abisbenzylisoquinoline alkaloid with anticancer potential, by formulating poly(lactic-co-glycolicacid) (PLGA) nanoparticles incorporated into a thermosensitive in situ gel (poloxamer 407).Nanoparticles were optimized via Box–Behnken design and characterized for physicochemicalproperties, exhibiting 169– 846 nm particle size, -31.9 to -19.9 mV zeta potential, highentrapment efficiency, and spherical morphology. FTIR, DSC, and XRD confirmed no drug–polymer interaction. The in situ gel showed suitable gelation temperature, pH, viscosity, andsustained in vitro release, with nanoparticle-loaded gel achieving prolonged drug releasecompared to plain drug gel. Ex vivo permeation across goat nasal mucosa demonstrated superiorpermeation for nanoparticle formulations. Cytocompatibility and hemolysis studies indicatedgood biocompatibility. These findings suggest PLGA nanoparticle–loaded in situ gel as apromising nasal delivery system for sustained tetrandrine release and potential improvement inglioblastoma therapy.