Hindered transport of spherical macromolecules in fibrous membranes and gels

Phillips, Ronald J.; Deen, William M.; Brady, John F.

doi:10.1002/aic.690351102

Cited by 145 publications

(155 citation statements)

References 28 publications

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“…However, this assumes that the transport of the 69 kDa protein with a hydraulic radius of 7.2 nm is comparable to polymeric nanoparticles with much lager radii. Theories of hindered transport in porous media suggest that the mobility of a freely suspended particle decreases as the ratio of particle size to effective pore size increases [37,16,18]. The present results for nanoparticles and previous results for liposomes indicate that the ECM significantly hinders transport of these particles, and that particle transport can be enhanced by osmotic dilation of the ECM.…”

Section: Discussionsupporting

confidence: 70%

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

et al. 2007

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This study investigates methods of manipulating the brain extracellular matrix (ECM) to enhance the penetration of nanoparticle drug carriers in convection-enhanced delivery (CED). A probe was fabricated with two independent microfluidic channels to infuse, either simultaneously or sequentially, nanoparticles and ECM-modifying agents. Infusions were performed in the striatum of the normal rat brain. Monodisperse polystyrene particles with a diameter of 54 nm were used as a model nanoparticle system. Because the size of these particles is comparable to the effective pore size of the ECM, their transport may be significantly hindered compared with the transport of low molecular weight molecules. To enhance the transport of the infused nanoparticles, we attempted to increase the effective pore size of the ECM by two methods: dilating the extracellular space and degrading selected constituents of the ECM. Two methods of dilating the extracellular space were investigated: co-infusion of nanoparticles and a hyperosmolar solution of mannitol, and pre-infusion of an isotonic buffer solution followed by infusion of nanoparticles. These treatments resulted in an increase in the nanoparticle distribution volume of 50% and 123%, respectively. To degrade hyaluronan, a primary structural component of the brain ECM, a pre-infusion of hyaluronidase (20,000 U/mL) was followed after 30 min by infusion of nanoparticles. This treatment resulted in an increase in the nanoparticle distribution of 64%. Our results suggest that both dilation and enzymatic digestion can be incorporated into CED protocols to enhance nanoparticle penetration.

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Section: Discussionsupporting

confidence: 70%

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

et al. 2007

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“…The average particle velocity is then divided by the average fluid velocity to form the convective transport coefficient. As shown above our results exhibit very good agreement with the results of Phillips et al, 1989 [5]. The differences are due to the fact that Phillips et al used spheres to construct their cylinders and in this LDRD/ER cylinders were explicitly used and the new capability did not have lubrication correction for tangential approach to a cylinder.…”

Section: Species Transport (Convective Transport Coefficient)supporting

confidence: 83%

Dynamic simulation tools for the analysis and optimization of novel collection, filtration and sample preparation systems

Clague¹,

Weisgraber²,

Rockway³

et al. 2006

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“…Solute behavior in hydrogels has been explained in terms of reduction in hydrogel free volume [20,21,22], enhanced hydrodynamic drag on the solute [23,24], increased path length due to obstruction [25,26], and a combination of hydrodynamic drag and obstruction effects [27].…”

Section: Amsden's Obstruction Scaling Theorymentioning

confidence: 99%

Effect of Cross-Linking on the Diffusion of Water, Ions, and Small Molecules in Hydrogels

2009

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Understanding the diffusion of small molecules in hydrogel system is of major importance in a variety of applications including drug delivery systems, tissue engineering and contact lens. Cross-linking density of hydrogels has been commonly used to tune key parameters like mesh size and molecular weight between cross-linkers, in order to change macroscopic properties of hydrogels. In this thesis, molecular dynamics investigations of chemically-cross-linked poly(ethylene glycol) (PEG) hydrogels are reported with the aim of exploring the diffusion properties of water, ions, and rhodamine within the polymer at the molecular level.The water structure and diffusion properties were studied at various cross-linking densities with molecular weights of the chains ranging from 572 to 3400. As the cross-linking density is increased, the water diffusion decreases and the slowdown in diffusion is more severe at the polymer-water interface. The water diffusion at various cross-linking densities is correlated with the water hydrogen bonding dynamics. The diffusion of ions and rhodamine also decreased as the cross-linking density is increased. The variation of diffusion coefficient with cross-linking density is related to the variation of water content at different cross-linking densities.Comparison of simulation results and obstruction scaling theory for hydrogels showed similar trends.ii To Father and Mother.iii

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Hindered transport of spherical macromolecules in fibrous membranes and gels

Cited by 145 publications

References 28 publications

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

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

Dynamic simulation tools for the analysis and optimization of novel collection, filtration and sample preparation systems

Effect of Cross-Linking on the Diffusion of Water, Ions, and Small Molecules in Hydrogels

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