Modeling of microvascular permeability changes after electroporation
Selma Corovic1, Bostjan Markelc2, Mitja Dolinar1
1University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Biocybernetics, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.
Plos One
|March 21, 2015
Summary
Electroporation temporarily increases blood vessel wall permeability, allowing macromolecules like therapeutic agents to extravasate. This study quantifies this effect, aiding the development of targeted drug delivery models.
Area of Science:
- Biomedical Engineering
- Vascular Biology
- Pharmacokinetics
Background:
- The vascular endothelium regulates the passage of substances from blood to tissues.
- Understanding macromolecule transport is crucial for targeted drug delivery.
Purpose of the Study:
- To quantify the increase in blood vessel wall permeability induced by electroporation for macromolecules.
- To simulate the extravasation of therapeutic molecules using dextran models.
Main Methods:
- Combined mathematical modeling (pharmacokinetic and finite element) with in vivo intravital fluorescence microscopy.
- Investigated extravasation of 70 kDa and 2000 kDa fluorescently labeled dextran molecules.
- Quantified transvascular transport by calculating apparent diffusion coefficients (D [μm²/s]).
Main Results:
- Calculated apparent diffusion coefficients for 70 kDa dextran: D = 0.0086 μm²/s.
- Calculated apparent diffusion coefficients for 2000 kDa dextran: D = 0.0045 μm²/s.
- Demonstrated electroporation-induced increase in microvessel wall permeability.
Conclusions:
- Electroporation enhances macromolecule extravasation across the blood vessel wall.
- Results support the development of predictive mathematical models for electroporation-mediated drug delivery.
- Findings have implications for delivering large therapeutic molecules like antibodies and plasmid DNA.
