Chronic, intermittent convection-enhanced delivery devices

Abstract

Background: Intraparenchymal convection-enhanced delivery (CED) of therapeutics directly into the brain has long been endorsed as a medium through which meaningful concentrations of drug can be administered to patients, bypassing the blood brain barrier. The translation of the technology to clinic has been hindered by poor distribution not previously observed in smaller pre-clinical models. In part this was due to the larger volumes of target structures found in humans but principally the poor outcome was linked to reflux (backflow) of infusate proximally along the catheter track. Over the past 10 years, improvements have been made to the technology in the field which has led to a small number of commercially available devices containing reflux inhibiting features.

New method: While these devices are currently suitable for acute or short term use, several indications would benefit from longer term repeated, intermittent administration of therapeutics (Parkinson's, Alzheimer's, Amyotrophic lateral sclerosis, Brain tumours such as Glioblastoma Multiforme (GBM) and Diffuse intrinsic Pontine Glioma (DIPG), etc.).

Results: Despite the need for a chronically accessible platform for such indications, limited experience exists in this part of the field.

Comparison with existing method(s): At the time of writing no commercially available clinical platform, indicated for chronic, intermittent or continuous delivery to the brain exists.

Conclusions: Here we review the improvements that have been made to CED devices over recent years and current state of the art for chronic infusion systems.

Keywords: Catheter; Chronic; Convection-enhanced delivery (CED); Intermittent; Optimisation.