Design and evaluation of PLGA-based hybrid nanoparticles for nasal paclitaxel delivery: formulation optimization, barrier transport, and cytotoxicity assessment

Paclitaxel (PTX) is a potent antiglioma agent, but its clinical use is limited by poor penetration across the blood–brain barrier (BBB). This study developed and evaluated a nose-to-brain delivery strategy using paclitaxel-loaded hybrid nanoparticles (HNP–PTX) for intranasal administration. A full 2² factorial design was employed to optimize the formulation, yielding an HNP–PTX system with a monodisperse distribution (<200 nm) and spherical morphology. The impact of chitosan coating was evaluated, revealing changes in surface charge and spray properties; but this did not significantly enhance transport across RPMI-2650 cells cultured at the air–liquid interface. Importantly, all HNP–PTX formulations preserved nasal epithelial barrier integrity while significantly increasing PTX permeation relative to the free drug. Cytotoxicity assays in U87-MG glioblastoma cells showed that HNP–PTX reduced cell viability more than both taxol and temozolomide (TMZ). These in vitro findings suggest HNP–PTX is a promising candidate for further in vivo evaluation as an intranasal formulation for glioblastoma treatment.