scholarly journals Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors

2021 ◽  
Author(s):  
Mostafa Sefidgar ◽  
M Soltani ◽  
Kaamran Raahemifar ◽  
Hossein Bazmara ◽  
Seyed Mojtaba Mousavi Nayinian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Solute Transport ◽  
Solid Tumor ◽  
Drug Concentration ◽  
Interstitial Fluid ◽  
Initial Conditions ◽  
Surrounding Tissue ◽  
Governing Equations ◽  
Tumor Shape

Background The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor. Methods The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated. Results Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible. Conclusions This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection.

scholarly journals Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors

2021 ◽  
Author(s):  
Mostafa Sefidgar ◽  
M Soltani ◽  
Kaamran Raahemifar ◽  
Hossein Bazmara ◽  
Seyed Mojtaba Mousavi Nayinian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Solute Transport ◽  
Solid Tumor ◽  
Drug Concentration ◽  
Interstitial Fluid ◽  
Initial Conditions ◽  
Surrounding Tissue ◽  
Governing Equations ◽  
Tumor Shape

Background The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor. Methods The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated. Results Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible. Conclusions This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection.

scholarly journals Brain solute transport is more rapid in periarterial than perivenous spaces

2021 ◽  
Author(s):  
Vegard Vinje ◽  
Erik Nicolaas Theodorus Petrus Bakker ◽  
Marie E Rognes
Keyword(s):  
Fluid Flow ◽  
Solute Transport ◽  
Interstitial Fluid ◽  
Computational Modelling ◽  
Perivascular Spaces ◽  
Tracer Transport ◽  
Csf Flow ◽  
Arrival Times ◽  
Open Question ◽  
Rapid Appearance

Background: Perivascular fluid flow, of cerebrospinal or interstitial fluid in spaces surrounding brain blood vessels, is recognized as a key component underlying brain transport and clearance. An important open question is how and to what extent differences in vessel type or geometry affect perivascular fluid flow and transport. Methods: Using computational modelling in both idealized and image-based geometries, we study and compare fluid flow and solute transport in pial (surface) periarterial and perivenous spaces. Results: Our findings demonstrate that differences in geometry between arterial and venous pial perivascular spaces (PVSs) lead to higher net CSF flow, more rapid tracer transport and earlier arrival times of injected tracers in periarterial spaces compared to perivenous spaces. Conclusions: These findings can explain the experimentally observed rapid appearance of tracers around arteries, and the delayed appearance around veins without the need of a circulation through the parenchyma, but rather by direct transport along the PVSs.

scholarly journals Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

2021 ◽  
Author(s):  
Barbara Bachmann ◽  
Sarah Spitz ◽  
Christian Jordan ◽  
Patrick Schuller ◽  
Heinz D Wanzenboeck ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Immune Cell ◽  
Scientific Progress ◽  
Morphological Characteristics ◽  
Interstitial Fluid Flow

After decades of simply being referred to as the body's sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for cancer, infections, and inflammatory diseases. However, the lack of cell-based assays capable of recapitulating the required biological complexity combined with unreliable in vivo animal models currently hamper scientific progress in lymph-targeted drug delivery. To gain more in-depth insight into the blood-lymph interface, we established an advanced chip-based microvascular model to study mechanical stimulation's importance on lymphatic sprout formation. Our microvascular model's key feature is the co-cultivation of spatially separated 3D blood and lymphatic vessels under controlled, unidirectional interstitial fluid flow while allowing signaling molecule exchange similar to the in vivo situation. We demonstrate that our microphysiological model recreates biomimetic interstitial fluid flow, mimicking the route of fluid in vivo, where shear stress within blood vessels pushes fluid into the interstitial space, which is subsequently transported to the nearby lymphatic capillaries. Results of our cell culture optimization study clearly show an increased vessel sprouting number, length, and morphological characteristics under dynamic cultivation conditions and physiological relevant mechanobiological stimulation. For the first time, a microvascular on-chip system incorporating microcapillaries of both blood and lymphatic origin in vitro recapitulates the interstitial blood-lymph interface.

Transient interstitial fluid flow in brain tumors: Effect on drug delivery

2005 ◽  
Vol 60 (17) ◽  
pp. 4803-4821 ◽  
Author(s):  
Chee Seng Teo ◽  
Wilson Hor Keong Tan ◽  
Timothy Lee ◽  
Chi-Hwa Wang
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Brain Tumors ◽  
Interstitial Fluid ◽  
Interstitial Fluid Flow

Fluid Flow Behaviour in Microneedle Arrays

2005 ◽  
Author(s):  
A. N. San ◽  
R. Ben Mrad ◽  
P. Sullivan
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Cross Sections ◽  
Transdermal Drug Delivery ◽  
Interstitial Fluid ◽  
Flow Behaviour ◽  
Electrokinetic Effect ◽  
Microneedle Arrays ◽  
Minor Losses ◽  
Array Geometry

This paper examines the geometries of basic straight microneedle arrays, slanted channel arrays with varying angles, and arrays with diverging and converging interior cross sections for the purpose of interstitial fluid extraction and transdermal drug delivery. Flow behaviour is analyzed under biometric pressure driven conditions including frictional losses, minor losses due to the array geometry, and losses due to electrokinetic effect in microchannels. This paper also presents design and fabrication details of preliminary work that will lead to a design for microneedle arrays.

scholarly journals Effect of Fluid Friction on Interstitial Fluid Flow Coupled with Blood Flow through Solid Tumor Microvascular Network

2021 ◽  
Author(s):  
Mostafa Sefidgar ◽  
M. Soltani ◽  
Kaamran Raahemifar ◽  
Hossein Bazmara
Keyword(s):  
Blood Flow ◽  
Porous Media ◽  
Fluid Flow ◽  
Solid Tumor ◽  
Interstitial Fluid ◽  
Brinkman Model ◽  
Fluid Friction ◽  
Darcy Model ◽  
Flow Through ◽  
Interstitial Velocity

A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

scholarly journals Effect of Fluid Friction on Interstitial Fluid Flow Coupled with Blood Flow through Solid Tumor Microvascular Network

2021 ◽  
Author(s):  
Mostafa Sefidgar ◽  
M. Soltani ◽  
Kaamran Raahemifar ◽  
Hossein Bazmara
Keyword(s):  
Blood Flow ◽  
Porous Media ◽  
Fluid Flow ◽  
Solid Tumor ◽  
Interstitial Fluid ◽  
Brinkman Model ◽  
Fluid Friction ◽  
Darcy Model ◽  
Flow Through ◽  
Interstitial Velocity

A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

scholarly journals A thermoporoelastic model for fluid transport in tumour tissues

2019 ◽  
Vol 16 (154) ◽  
pp. 20190030 ◽  
Author(s):  
Assunta Andreozzi ◽  
Marcello Iasiello ◽  
Paolo Antonio Netti
Keyword(s):  
Fluid Flow ◽  
Heat Source ◽  
Interstitial Fluid ◽  
Fluid Transport ◽  
Governing Equations ◽  
Tumour Blood Flow ◽  
Finite Element Scheme ◽  
Scaling Parameters ◽  
Thermal Dilation ◽  
Physical Phenomena

In this paper, the effect of coupled thermal dilation and stress on interstitial fluid transport in tumour tissues is evaluated. The tumour is modelled as a spherical deformable poroelastic medium embedded with interstitial fluid, while the transvascular fluid flow is modelled as a uniform distribution of fluid sink and source points. A hyperbolic-decay radial function is used to model the heat source generation along with a rapid decay of tumour blood flow. Governing equations for displacement, fluid flow and temperature are first scaled and then solved with a finite-element scheme. Results are compared with analytical solutions from the literature, while results are presented for different scaling parameters to analyse the various physical phenomena. Results show that temperature affects pressure and velocity fields through the deformable medium. Finally, simulations are performed by assuming that the heat source is periodic, in order to assess the extent to which this condition affects the velocity field. It is reported that in some cases, especially for periodic heating, the combination of thermoelastic and poroelastic deformation led to no monotonic pressure distribution, which can be interesting for applications such as macromolecule drug delivery, in which the advective contribution is very important owing to the low diffusivity.

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