Modeling of microvascular permeability changes after electroporation

PloS One
Selma ČorovićTomaz Jarm

Abstract

Vascular endothelium selectively controls the transport of plasma contents across the blood vessel wall. The principal objective of our preliminary study was to quantify the electroporation-induced increase in permeability of blood vessel wall for macromolecules, which do not normally extravasate from blood into skin interstitium in homeostatic conditions. Our study combines mathematical modeling (by employing pharmacokinetic and finite element modeling approach) with in vivo measurements (by intravital fluorescence microscopy). Extravasation of fluorescently labeled dextran molecules of two different sizes (70 kDa and 2000 kDa) following the application of electroporation pulses was investigated in order to simulate extravasation of therapeutic macromolecules with molecular weights comparable to molecular weight of particles such as antibodies and plasmid DNA. The increase in blood vessel permeability due to electroporation and corresponding transvascular transport was quantified by calculating the apparent diffusion coefficients for skin microvessel wall (D [μm2/s]) for both molecular sizes. The calculated apparent diffusion coefficients were D = 0.0086 μm2/s and D = 0.0045 μm2/s for 70 kDa and 2000 kDa dextran molecules, res...Continue Reading

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Citations

Jan 21, 2016·Biophysical Journal·Mohammad BonakdarRafael V Davalos
Mar 21, 2020·Expert Opinion on Drug Delivery·Janja Dermol-ČerneDamijan Miklavčič
Jun 23, 2016·Advanced Healthcare Materials·Hasan E AbaciAngela M Christiano

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Methods Mentioned

BETA
confocal microscopy
fluorescence microscopy

Software Mentioned

Comsol Multiphysics
AxioVision
Matlab

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