Design and Evaluation of PLGA-Based Hybrid Nanoparticles for Nasal Paclitaxel Delivery: Formulation Optimization, Barrier Transport, and Cytotoxicity Assessment
TL;DR
HNP–PTX is a promising candidate for further in vivo evaluation as an intranasal formulation for glioblastoma treatment and Cytotoxicity assays showed that HNP–PTX reduced cell viability more than both taxol and temozolomide (TMZ).
Abstract
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.