Convection-Enhanced Drug Delivery in Central Nervous System Tumors

Convection-enhanced delivery (CED) is a targeted infusion technique designed to bypass the blood–brain barrier and achieve high local concentrations of therapeutic agents within central nervous system tumours. By applying a controlled positive pressure gradient, CED drives infusate through the interstitial spaces of the tumour and surrounding parenchyma, producing a more uniform drug distribution than diffusion-limited methods. Over the past decade, advances in catheter design, reflux-inhibiting technologies and real-time imaging guidance have improved both the precision and safety of CED. Nanocarriers such as liposomes and polymeric nanoparticles have further enhanced drug stability and retention, while incorporation of radioisotopes and targeted toxins has expanded the therapeutic repertoire. Despite promising preclinical results, clinical translation has been hindered by variable infusion volumes, backflow along catheter tracks and complex tumour microenvironmental factors such as interstitial fluid flow and tissue anisotropy. Recent efforts focus on optimising infusion parameters, understanding patient-specific anatomy through imaging-based modelling, and integrating continuous or repeated delivery systems to achieve sustained therapeutic exposure. Collectively, these developments underscore the potential of CED to transform the management of inoperable or recurrent brain tumours, offering renewed prospects for improving survival and quality of life.

Research from Nature Portfolio

Recent studies have evaluated nanoliposome-encapsulated radioisotopes in recurrent high-grade glioma. In a first-in-human phase 1 trial, patients received escalating doses of a rhenium-186 chelated nanoliposome via CED. The procedure was well tolerated up to the highest administered activity, with no dose-limiting toxicities observed. Dosimetric analysis revealed that infusions exceeding an absorbed tumour dose threshold yielded median overall survival and progression-free survival intervals that surpassed historical benchmarks for recurrent glioblastoma. Crucially, enhanced tumour control correlated with the volume of tissue covered and the radiation dose delivered per unit volume. These findings establish a safety profile for radio-nanoliposomes in CED and highlight the importance of precise dose delivery and distribution mapping in future efficacy trials.

Convection-Enhanced Drug Delivery in Central Nervous System Tumors publication trend

The graph below shows the total number of articles in convection-enhanced drug delivery in central nervous system tumors across all publications each year (not limited to Nature Index journals).

Technical terms

Convection-Enhanced Delivery (CED): A direct infusion technique using positive pressure to drive drugs through extracellular spaces, bypassing the blood–brain barrier.

Blood–Brain Barrier (BBB): A selective endothelial interface that restricts passage of substances from the bloodstream into brain tissue.

Nanoliposome: A nanoscale lipid vesicle used to encapsulate and transport therapeutic agents, enhancing stability and targeted release.

Interstitial Fluid Flow (IF flow): Movement of fluid within tissue extracellular spaces, influencing drug transport and tissue biomechanics.

Maximum Tolerated Dose (MTD): The highest dose of a therapy that does not produce unacceptable side effects in patients.

Progression-Free Survival (PFS): The duration during which a patient’s disease does not exhibit growth or spread following treatment.

References

1. Convection enhanced delivery of Rhenium (186Re) Obisbemeda (186RNL) in recurrent glioma: a multicenter, single arm, phase 1 clinical trial. Nature Communications (2025).
2. Treatment Strategies in Diffuse Midline Gliomas With the H3K27M Mutation: The Role of Convection-Enhanced Delivery in Overcoming Anatomic Challenges. Frontiers in Oncology (2019).
3. Convection‐Enhanced Delivery in Malignant Gliomas: A Review of Toxicity and Efficacy. Journal of Oncology (2019).
4. Convection-Enhanced Delivery: Connection to and Impact of Interstitial Fluid Flow. Frontiers in Oncology (2019).
5. Effect of tissue permeability and drug diffusion anisotropy on convection-enhanced delivery. Drug Delivery (2019).
6. Image-based predictive modelling frameworks for personalised drug delivery in cancer therapy. Journal of Controlled Release (2024).
7. Chronic, intermittent convection-enhanced delivery devices. Journal of Neuroscience Methods (2015).
8. Effect of Needle Insertion Speed on Tissue Injury, Stress, and Backflow Distribution for Convection-Enhanced Delivery in the Rat Brain. PLOS ONE (2014).