In vivo brain electrophoresis – a novel method for chemotherapy of CNS diseases

Abstract

Objective: The blood–brain barrier (BBB) is a protective mechanism that does its job superbly. So much so, that hitherto, brain chemotherapy has been limited by it. In fact, very few agents are effective against brain disease due to the inherent difficulties of penetrating the BBB. We describe a novel, extremely focused method for delivering drugs to specific diseased areas. This innovative method directly delivers putative substances to the pathological area, bypassing the BBB. Treatment of brain diseases could be improved by targeted, controlled delivery of therapeutic substances to diseased cerebral areas. Our described novel method – in vivo electrophoresis – achieves this.

Methods: This technique was evaluated in beagles after craniotomy was performed and a custom-designed plate with electrodes inserted. The delivery of charged substances to selected areas with predictably guided movement was achieved via a created electrical field. Gadolinium, a compound unable to cross the BBB, was injected intracerebrally whereas an electrical field was created using the implanted electrodes surrounding the injection area. The electrical field-guided Gadolinium movement was evaluated using MRI.

Results: Gadolinium was moved predictably using the created electrical field without complications.

Conclusions: The experiment successfully demonstrated controlled movement of the substance. This technique can significantly change treatment of brain diseases because substances: i) may be moved in a controlled, predictable way – exponentially increasing therapeutic interactions with the target; and ii) no longer need to conform to constraints dictated by the BBB (molecular mass < 500 d; lipophilic), thereby increasing potential number of usable substances.

Keywords:

• blood–brain barrier
• drug delivery
• glioblastoma multiforme
• in vivo electrophoresis
• novel method
• stereotactic chemotherapy

Declaration of interest

The authors disclose involvement in a clinical trial IACUC protocol 2013A00000001.The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.