Locally implantable nanofibre meshes by sustained release of temozolomide for combined thermo-chemotherapy to treat glioblastoma

Abstract

Glioblastoma (GBM) is a highly malignant type of brain tumour that arises from astrocytes or supportive brain tissue in adults. Although there are several therapeutic options, recurrence rates remain high, with a 5 year survival rate expectancy of less than 10%. This study investigates nanofibre meshes that enable the long-term release of temozolomide (TMZ) over a 4 week period by controlling the fibre morphologies. The nanofibre meshes were fabricated via the electrospinning of a biodegradable polymer, poly(ε-caprolactone) (PCL). The obtained meshes were flexible and implantable as a local intracranial drug delivery platform. The nanofibre meshes also carry magnetic nanoparticles (MNPs) that enable the combined therapy of hyperthermia/chemotherapy corresponding to an alternating magnetic field (AMF). The heat generation behaviour of the nanofibre meshes was successfully adjusted in a hyperthermic temperature range (∼42.6 °C). The TMZ/MNP-loaded nanofibre meshes showed a 76% reduction in the cell viability of GBM cancer (T98G) cells through the synergistic effect of hyperthermia and chemotherapy. These results indicated the potential applications of nanofibre meshes as an implantable intracranial drug delivery system as an adjunct to surgery and radiation for GBM patients.