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Modeling of microvascular permeability changes after electroporation.

Corovic S, Markelc B, Dolinar M, Cemazar M, Jarm T - PLoS ONE (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Biocybernetics, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.

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.

No MeSH data available.


Related in: MedlinePlus

Sensitivity analysis of the calculated apparent diffusion coefficient Dwall.Sensitivity analysis of apparent diffusion coefficient Dwall for 70 kDa and 2000 kDa FD to the values of Dtiss over the range from 2 μm2/s to 70 μm2/s. Dwall(Dtiss) functions calculated for 70 kDa and 2000 kDa FD are represented with red and blue curves, respectively. The bold curves represent the median values of Dwall.
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pone.0121370.g007: Sensitivity analysis of the calculated apparent diffusion coefficient Dwall.Sensitivity analysis of apparent diffusion coefficient Dwall for 70 kDa and 2000 kDa FD to the values of Dtiss over the range from 2 μm2/s to 70 μm2/s. Dwall(Dtiss) functions calculated for 70 kDa and 2000 kDa FD are represented with red and blue curves, respectively. The bold curves represent the median values of Dwall.

Mentions: The results of sensitivity analysis showed that the calculated Dwall values were not sensitive to the values of the tissue diffusion coefficients Dtiss over a wide range from 2 μm2/s to 70 μm2/s (Fig. 7).


Modeling of microvascular permeability changes after electroporation.

Corovic S, Markelc B, Dolinar M, Cemazar M, Jarm T - PLoS ONE (2015)

Sensitivity analysis of the calculated apparent diffusion coefficient Dwall.Sensitivity analysis of apparent diffusion coefficient Dwall for 70 kDa and 2000 kDa FD to the values of Dtiss over the range from 2 μm2/s to 70 μm2/s. Dwall(Dtiss) functions calculated for 70 kDa and 2000 kDa FD are represented with red and blue curves, respectively. The bold curves represent the median values of Dwall.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368817&req=5

pone.0121370.g007: Sensitivity analysis of the calculated apparent diffusion coefficient Dwall.Sensitivity analysis of apparent diffusion coefficient Dwall for 70 kDa and 2000 kDa FD to the values of Dtiss over the range from 2 μm2/s to 70 μm2/s. Dwall(Dtiss) functions calculated for 70 kDa and 2000 kDa FD are represented with red and blue curves, respectively. The bold curves represent the median values of Dwall.
Mentions: The results of sensitivity analysis showed that the calculated Dwall values were not sensitive to the values of the tissue diffusion coefficients Dtiss over a wide range from 2 μm2/s to 70 μm2/s (Fig. 7).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Biocybernetics, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.

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.

No MeSH data available.


Related in: MedlinePlus