Author/Editor		Čorović, Selma; Markelc, Boštjan; Dolinar, Mitja; Čemažar, Maja; Jarm, Tomaž
Title		Modeling of microvascular permeability changes after electroporation
Type		članek
Publication year		2015
ISSN		1932-6203 - PloS one
Language		eng
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 [%m2/s]) for both molecular sizes. The calculated apparent diffusion coefficients were D = 0.0086 %m2/s and D = 0.0045 %m2/s for 70 kDa and 2000 kDa dextran molecules, respectively. The results of our preliminary study have important implications in development of realistic mathematical models for prediction of extravasation and delivery of large therapeutic molecules to target tissues by means of electroporation.
Keywords		elektroporacija permeabilnost mikrožilna prepustnost krvne žile electroporation permeability microvascular permeability blood vessels