Biomedical engineering approaches to enhance therapeutic delivery for malignant glioma.

We review the challenges of next-generation therapeutics for both systemic and localised delivery to brain tumours and discuss how recent engineering advances may be used to enhance brain penetration of systemic delivery therapies. The unmet clinical need which drug delivery seeks to address is discussed with reference to the therapy obstacles that the intra-tumour heterogeneity of glioma present. The unmet chemistry and biomedical engineering challenge to develop controlled release therapeutics is appraised, with commentary on current success/failures in systemic carrier-mediated delivery, including receptor-targeted, cell-based, blood-brain-barrier disrupting and MRI-guided focused ultrasound. Localised therapeutic delivery is a relatively under-studied research avenue and is discussed with reference to existing technologies in preclinical development. These include convection-enhanced delivery, alternative catheter delivery, and neuro-surgically applied delivery systems such as polymeric hydrogels and interstitial spray. A myriad of nano-scale therapeutic delivery systems is emerging as potential future medicines for malignant brain tumours. Such biomedically-engineered systems will increasingly feature in next-generation neuro-oncological clinical trials to deliver repurposed and experimental therapeutics, aimed at achieving therapeutic drug concentrations in the brain, with associated mortality and morbidity benefits for patients.