title: Biphasic finite element model of solute transport for direct infusion into nervous tissue.
abstract: Infusion-based techniques are promising drug delivery methods for treating diseases of the nervous system. Direct infusion into tissue parenchyma circumvents the blood-brain barrier, localizes delivery, and facilitates transport of macromolecular agents. Computational models that predict interstitial flow and solute transport may aid in protocol design and optimization. We have developed a biphasic finite element (FE) model that accounts for local, flow-induced tissue swelling around an infusion cavity. It solves for interstitial fluid flow, tissue deformation, and solute transport in surrounding isotropic gray matter. FE solutions for pressure-controlled infusion were validated by comparing with analytical solutions. The influence of deformation-dependent hydraulic permeability was considered. A transient, nonlinear relationship between infusion pressure and infusion rate was determined. The sensitivity of convection-dominated solute transport (i.e., albumin) over a range of nervous tissue properties was also simulated. Solute transport was found to be sensitive to pressure-induced swelling effects mainly in regions adjacent to the infusion cavity (r/a 0 <or= 5 where a 0 is the outer cannula radius) for short times infusion simulated (3 min). Overall, the biphasic approach predicted enhanced macromolecular transport for small volume infusions (e.g., 2 microL over 1 h). Solute transport was enhanced by decreasing Young's modulus and increasing hydraulic permeability of the tissue.
authors.affiliation: Department of Mechanical and Aerospace Engineering, 212 MAE-A, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.forename: Malisa
authors.initials: M
authors.lastname: Sarntinoranont
mesh_terms: D001693:Biological Transport, Active / Q000502:physiology*; D003198:Computer Simulation; D020342:Finite Element Analysis; D007263:Infusions, Parenteral / Q000379:methods*; D044085:Microfluidics / Q000379:methods*; D008959:Models, Neurological; D009417:Nerve Tissue / Q000378:metabolism*; D010599:Pharmacokinetics; D012995:Solubility