129 Electroactive drug delivery for local glioblastoma treatment

Vollständiger Abstract

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Abstract Introduction Despite recent advances in cancer therapeutics, the prognosis for glioblastoma remains exceptionally poor, stemming from the limited ability of systemically administered chemotherapeutics to cross the blood brain barrier (BBB). Mechanically circumventing the BBB represents a promising avenue. However, biomaterials previously used for local delivery suffer from low control over drug release, further limiting their translation. To address this, an implantable bioelectronic drug delivery device was developed to enable targeted, ‘on demand’ voltage-controlled solid-phase drug release. The device is designed to be compatible with neurosurgical workflows Method Drug release from the device is triggered by externally applying +2V (DC) to the device for 0.5 h. Voltage-triggered release of doxorubicin has been quantified using fluorospectrometric techniques. The cytotoxic (CellTiterGlo) and metabolic effects (liquid chromatography mass spectrometry) of voltage-triggered drug release from the device have been investigated in a 2D and 3D patient derived glioblastoma models. Devices were also implanted in vivo in an orthotopic mouse model (SB28) during the terminal surgery, with the brains cryosectioned to assess spread of doxorubicin. Results Voltage-mediated cytotoxicity of doxorubicin has been demonstrated in 2D and 3D patient derived glioblastoma models, with safety of the material and electrical stimulation alone confirmed in vitro. Further, release into mouse brain tumours confirmed greater doxorubicin diffusion under active release, a finding also confirmed in a similar study but in agarose gel brain tissue phantoms. Conclusions This device shows promise for targeted, ‘dry’ delivery of a chemotherapeutic drug within a short time window (0.5h). Plans are underway to commence a pilot in vivo study to investigate the safety and efficacy of this device in an SB28 orthotopic mouse brain tumour model.