Implantable Polyurethane Scaffolds Loading with PEG-Paclitaxel Conjugates for the Treatment of Glioblastoma Multiforme

Improvement of the treatment for Glioblastoma multiforme(GBM)especially the development of in situ controllable drug release is still a major concern.In this study,we developed waterborne biodegradable polyurethane(WBPU)scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel(PTX)polymer-drug conjugates(PDCs)for targeted GBM therapy in situ.The drug scaffolds could be implanted at residual GBM site post-operation.Dual-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX,poly(ethylene glycol)(PEG),and arginine-glycine-aspartic acid(RGD).The RGD-modified PTX-PDCs were spherical nanoparticles(NPs)that would be released from scaffolds and identified GBM cells actively.Internalized redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione(GSH).The release profiles of PTX from the scaffolds with/without GSH were investigated.In vitro cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells,suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain injury.In vivo anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing apoptosis.In general,the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously,indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM.