title: Modeling of microvascular permeability changes after electroporation.
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, 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.
authors: University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Biocybernetics, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.
authors: Selma
authors: S
authors: Corovic
authors: Institute of Oncology Ljubljana, Department of Experimental Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia.
authors: Bostjan
authors: B
authors: Markelc
authors: University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Biocybernetics, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.
authors: Mitja
authors: M
authors: Dolinar
authors: Institute of Oncology Ljubljana, Department of Experimental Oncology, Zaloska 2, SI-1000 Ljubljana, Slovenia; University of Primorska, Faculty of Health Sciences, Polje 42, SI-6310 Izola, Slovenia.
authors: Maja
authors: M
authors: Cemazar
authors: University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Biocybernetics, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.
authors: Tomaz
authors: T
authors: Jarm
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D003911:Dextrans / Q000378:metabolism; D004058:Diffusion; D018274:Electroporation / Q000379:methods*; D005453:Fluorescence; D007091:Image Processing, Computer-Assisted; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000502:physiology*; D008954:Models, Biological; D013997:Time Factors
chemical_list: D003911:Dextrans