Alice Hagen
Biocompatibles UK Ltd, UK
Title: Novel drug-eluting beads (DEBs) containing tyrosine kinase inhibitors (TKIs) for cancer therapy
Biography
Biography: Alice Hagen
Abstract
DEBs are embolic agents that can be loaded with anti-cancer drugs, which are subsequently released over time at the tumour site following administration into the arteries that feed liver malignacies, using a technique known as transarterial chemoembolisation (TACE). The most commonly loaded drugs into DEB are doxorubicin and irinotecan, both cytotoxic agents that interfere with DNA replication. However, it is also possible to load DEB with certain targeted agents such as TKIs. Due to the chemical structure and properties of these compounds, it is necessary to use different methodological approaches to incorporate them into the bead matrix. We describe the loading of DC Bead™ with vandetanib, an antiangiogenic multi-targeted TKI. The molecule may exist in several pH-dependent charge states, which affects both its solubility in water and capacity to occupy drug binding sites within the beads. Maximum drug loading capacity of vandetanib into DC Bead™ and a novel radiopaque version was investigated at varying pH. Uniform distribution of the drug throughout the bead was confirmed by SEM-EDX analysis. The effect of drug loading on physicochemical properties of the beads such as size, radiopacity and compressibility was examined, as well as the characteristics of in vitro drug release. In order to mimic ischaemia after embolization, the effect of vandetanib on HepG2 cell viability under hypoxic conditions was investigated by MTT assay. Vandetanib showed equipotency in hypoxia and normoxia across a range of concentrations, with an IC50 of approximately 6.25µM, confirming its suitability for delivery from a DEB.
