Abstract
Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumour, which is associated with a poor two-year survival rate and a high rate of fatal recurrence near the original tumour. Focal/local drug delivery devices hold promise for improving therapeutic outcomes for GBM by increasing drug concentrations locally at the tumour site, or by facilitating the use of potent anti-cancer drugs that are poorly permeable across the blood brain barrier (BBB). For inoperable tumours, stereotactic delivery to the tumour necessitates the development of nanoscale/microscale injectable drug delivery devices. Herein we assess the ability of a novel class of polymer nanotube (based on poly(ethylene glycol) (PEG)) to load doxorubicin (a mainstay breast cancer therapeutic with poor BBB permeability) and release it slowly. The drug loading properties of the PEG nanotubes could be tuned by varying the degree of carboxylic acid functionalisation and hence the capacity of the nanotubes to electrostatically bind and load doxorubicin. 70% of the drug was released over the first seven days followed by sustained drug release for the remaining two weeks tested. Unloaded PEG nanotubes showed no toxicity to any of the cell types analysed, whereas doxorubicin loaded nanotubes decreased GBM cell viability (C6, U-87 and U-251) in a dose dependent manner in 2D in vitro culture. Finally, doxorubicin loaded PEG nanotubes significantly reduced the viability of in vitro 3D GBM models whilst unloaded nanotubes showed no cytotoxicity. Taken together, these findings show that polymer nanotubes could be used to deliver alternative anti-cancer drugs for local therapeutic strategies against brain cancers.
Highlights
Glioblastoma multiforme (GBM) is classi ed as a grade IV glioma by the World Health Organisation (WHO)[1] and is the most common and aggressive malignant brain tumour
The drug loading properties of the poly(ethylene glycol) (PEG) nanotubes could be tuned by varying the degree of carboxylic acid functionalisation and the capacity of the nanotubes to electrostatically bind and load doxorubicin. 70% of the drug was released over the first seven days followed by sustained drug release for the remaining two weeks tested
Polymer nanotubes comprised of poly(ethylene glycol) were successfully synthesised via a template synthesis procedure
Summary
Glioblastoma multiforme (GBM) is classi ed as a grade IV glioma by the World Health Organisation (WHO)[1] and is the most common and aggressive malignant brain tumour. Current therapeutic strategies result in a median survival rate that is less than two years.[2] Symptoms of GBM include thromboembolism, seizures, headaches, vision problems, memory loss and nausea/ vomiting.[3] The current treatment of newly diagnosed GBM patients utilises surgical resection of the tumour to relieve the symptoms, decrease the bulk of the tumour and to aid the diagnosis. Local delivery bypasses the blood brain barrier (BBB) enabling the utilisation of therapeutics that cannot cross
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