Coupled macromolecular transport and gel mechanics: Poroviscoelastic approach

Abstract

Designing drug delivery devices or drug delivery protocols poses problems because they are considered to operate in a mechanically static environment. It should consider, however, transport processes in these cases occur in a mechanically dynamic environment since mechanical stimuli may strongly influence transport within soft hydrated materials. A general framework combines fluid and macromolecular transport with the mechanics of hydrated polymer gels or tissue. As an example, the model equations have been created for a spherical geometry to describe the distribution of macromolecules within the gel resulting from a constant pressure or a constant flow infusion source. The model describes the overall average profiles of the interstitial fluid pressure, velocity and solid matrix dilatation, displacement, and stress, as well as macromolecular distribution. The basic theory provides new insight into understanding the transport of macromolecules within mechanically stimulated polymeric gets and tissues and, therefore, represents a valuable tool for designing and engineering novel drug delivery systems, as well as optimization of drug delivery protocols to be used in detection and treatments

Modeling of drug delivery into tissues with a microneedle array using mixture theory

“…Such data are used to compare with the simulation results in Lv et al (2006). As with Lv et al (2006), the simulations are also carried out with different initial volume fraction of fluid constituent, ϕ 0 f , and blood absorption coefficient, B. κ, λ s , Lames's coefficients λ s = 13.16 kPa, µ s = 6.5 kPa (Nicholson and Phillips 1981;Jain 1987;Netti et al 2003) Diffusion coefficients (Nicholson and Phillips 1981;Jain 1987;Netti et al 2003), and assumed to be constant.…”

A Biphasic Hyperelastic Model for the Analysis of Fluid and Mass Transport in Brain Tissue

“…Previous models of infusion into the brain and spinal cord have generally either considered (1) anatomically realistic geometry but assumed no tissue deformation during the infusion, 16,17,28,29 or (2) the concomitant tissue deformation and drug transport but for a simplified, spherical geometry. 8,22,24 To the best of our knowledge, no model has been proposed to consider simultaneously nonlinear stress-strain curves under finite deformation, nonlinear variation of hydraulic conductivity, and convective-diffusive transport of the infused agent. We present a spherically symmetric model of the concomitant fluid and mass transport that occurs during the large deformation of brain tissue as a result of convection-enhanced delivery.…”

“…2,3,31 Each of the biphasic studies, with the exception of the recent study by Dutta-Roy et al, 12 is limited by the assumption of linear elasticity of the solid phase. Initial attempts at modeling the mass transport that occurs during convection-enhanced delivery were conducted under the even more limiting assumption that the tissue is rigid during the infusion, 22,28,29 although this was relaxed by Netti et al 24 and Chen and Sarntinoranont, 8 who also assume linear elasticity of the solid phase.…”

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

“…A second method of increasing the effective pore size is to exploit the poroelasticity of healthy brain tissue [33] and tumors [55] by dilating the extracellular space. Infusing a hyperosmolar solution into the extracellular space produces a water flux out of surrounding blood vessels [40] and brain cells [22], which increases the porosity of the ECM.…”