Convection-Enhanced Delivery In Silico Study for Brain Cancer Treatment

Abstract

Brain cancer therapy remains a formidable challenge in oncology. Convection-enhanced delivery (CED) is an innovative and promising local drug delivery method for the treatment of brain cancer, overcoming the challenges of the systemic delivery of drugs to the brain. To improve our understanding about CED efficacy and drug transport, we present an in silico methodology for brain cancer CED treatment simulation. To achieve this, a three-dimensional finite element formulation is utilized which employs a brain model representation from clinical imaging data and is used to predict the drug deposition in CED regimes. The model encompasses biofluid dynamics and the transport of drugs in the brain parenchyma. Drug distribution is studied under various patho-physiological conditions of the tumor, in terms of tumor vessel wall pore size and tumor tissue hydraulic conductivity as well as for drugs of various sizes, spanning from small molecules to nanoparticles. Through a parametric study, our contribution reports the impact of the size of the vascular wall pores and that of the therapeutic agent on drug distribution during and after CED. The in silico findings provide useful insights of the spatio-temporal distribution and average drug concentration in the tumor towards an effective treatment of brain cancer.

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“…It is based on the positive pressure method and continuous infusion of the solution for a long time to maintain a constant pressure gradient and stimulate convection of the interstitial fluid in addition to the osmotic effect. CED requires only minimally invasive brain surgery [87,89,90] and can bypass the BBB by direct drug infusion into the interstitial space of the brain tumor through surgically placed catheters. Various types of therapeutic agents can be administered directly to a specific target area allowing large volumes of high-concentration drugs to be dispensed with minimal systemic toxicity.…”