Design of a dynamic optical tissue phantom to model drug extravasation pharmacokinetics

We describe an optical tissue phantom that enables the simulation of drug extravasation from microvessels. The phantom consists of a microdialysis tubing bundle, to simulate the permeable blood vessels, immersed in an aqueous suspension of titanium dioxide (TiO₂) to simulate tissue scattering. The intent is to facilitate testing of optical pharmacokinetics (OP) methods for monitoring local drug delivery to tissues in vivo, and to validate computational compartmental models of drug delivery. To simulate drug administration, an optical dye is circulated through the porous microdialysis tubing bundle. OP spectroscopy is used to measure changes in the absorption coefficient of the TiO₂ medium due to the arrival and diffusion of the dye. We have established time-dependent concentration profiles to compare the simulation of drug delivery by intravenous (IV) and intra-arterial (IA) routes. Additionally, pharmacokinetic compartmental models are implemented in computer simulations of drug extravasation from the blood vessels for the conditions studied within the phantom. The simulated concentration time-profiles agree well with measurements from the phantom. The results are encouraging for future optical pharmacokinetic method development, both physical and computational, to understand drug extravasation under various physiological conditions.