Convection Enhanced Delivery (CED) is a sophisticated method for administering therapeutic agents directly to specific areas, particularly within the brain. This advanced, highly targeted delivery system is designed to overcome anatomical barriers and achieve localized treatment effects.
Understanding Drug Delivery Challenges
Delivering therapeutic agents effectively to certain regions, especially the brain, presents challenges. The blood-brain barrier (BBB) is a highly selective physiological safeguard protecting the central nervous system from toxins and pathogens. Composed of tightly connected endothelial cells, this barrier restricts the passage of over 98% of potential therapeutic drugs from the bloodstream into brain tissue.
Traditional systemic drug administration, such as oral pills or intravenous injections, often results in widespread distribution throughout the body. This leads to insufficient drug concentrations at the brain’s target site. Systemic delivery also causes undesirable side effects due to toxicity in healthy tissues.
Even direct injections, which rely on passive diffusion, face limitations within dense tissues like the brain. Diffusion spreads drugs slowly and unevenly, typically only a few millimeters from the injection point. Achieving therapeutic concentrations across a larger volume through diffusion alone would require high initial drug concentrations, increasing local toxicity risk.
The Principles of Convection Enhanced Delivery
Convection Enhanced Delivery operates on a distinct principle compared to diffusion-based methods. Instead of passive movement, CED actively pushes therapeutic agents through tissue using continuous, positive pressure. This generates a bulk flow, carrying the drug through the brain’s interstitial spaces and displacing extracellular fluid.
The core mechanism involves precisely placing specialized, small-diameter catheters directly into the target region of the brain. These catheters are inserted through small burr holes, often guided by imaging techniques to ensure accurate positioning within the interstitial space. An external infusion pump is connected to the catheter, which then delivers the therapeutic agent at a controlled, continuous rate.
Infusion rates typically range from 0.1 to 10 microliters per minute, depending on the drug and target tissue. This sustained pressure creates a uniform and widespread distribution of the therapeutic agent throughout the desired volume within the brain. Convection allows for a more homogeneous delivery to larger tissue volumes, ensuring that a consistent concentration of the drug reaches the affected area. This pressure-driven flow bypasses the blood-brain barrier, enabling the delivery of larger molecules or those with poor diffusive properties directly to the central nervous system.
Current and Potential Medical Uses
Convection Enhanced Delivery is being extensively explored and applied in the treatment of various neurological conditions. A prominent application is in the management of brain tumors, such as glioblastoma, which are aggressive and notoriously difficult to treat due to the protective barrier and their infiltrative nature. CED allows direct delivery of anti-cancer agents to the tumor and surrounding infiltrated brain tissue.
This direct approach minimizes systemic side effects, as the drug’s exposure to the rest of the body is significantly reduced. For instance, in pediatric cases of diffuse intrinsic pontine glioma (DIPG), a challenging brainstem tumor, CED offers a promising avenue for delivering chemotherapy directly to the affected region, where other treatment options are limited. Clinical trials have investigated various agents, including immunomodulatory therapies and oncolytic viruses, for glioblastoma treatment via CED.
Beyond oncology, CED is also under investigation for neurodegenerative disorders, including Parkinson’s disease. For these conditions, CED facilitates the targeted delivery of neurotrophic factors or gene therapies that could protect neurons or restore function. The ability to deliver these therapeutic agents precisely to the affected brain regions holds promise for improving outcomes by directly addressing the localized pathology while limiting widespread drug exposure.