Extravasation of PEGylated Spherical Nanoparticles through a Circular Pore of Similar Size

In this paper, we study the extravasation of PEGylated spherical nanoparticles through a circular pore of similar size using theoretical, computational, and experimental methods. First, we develop a theoretical model for the extravasation of bare spheres and show how the extravasation rate depends on the particle size and the pore length. We conduct corresponding Brownian dynamics (BD) simulations, which corroborate our theory. Next, we build upon our model of bare spheres to include the effect of PEGylation. We conduct free-space BD simulations of PEGylated particles, where the tethered polymers are modeled as bead–spring chains, and determine the particle diffusivity. Using a Monte Carlo method, we construct the free energy field of the PEGylated particle in the pore, and we use this to develop an approximate theoretical model of extravasation. To corroborate our model, we conduct BD simulations in the free energy field and experimentally measure the extravasation rate of PEGylated MS2 through porous membranes. In the context of drug delivery, our work implies that approximating PEGylated particles as bare spheres with radius equal to the effective hydrodynamic radius may incorrectly overpredict extravasation rates.