scholarly journals Numerical Simulation of Particle Transport and Deposition in the Pulmonary Vasculature

2014 ◽  
Vol 136 (12) ◽  
Author(s):  
Salman Sohrabi ◽  
Junda Zheng ◽  
Ender A. Finol ◽  
Yaling Liu
Keyword(s):  
Blood Flow ◽  
Steady Flow ◽  
Particle Deposition ◽  
Drug Carriers ◽  
Pulmonary Vasculature ◽  
Flow Profile ◽  
Wide Range ◽  
Deposition Fraction ◽  
Particle Binding

To quantify the transport and adhesion of drug particles in a complex vascular environment, computational fluid particle dynamics (CFPD) simulations of blood flow and drug particulate were conducted in three different geometries representing the human lung vasculature for steady and pulsatile flow conditions. A fully developed flow profile was assumed as the inlet velocity, and a lumped mathematical model was used for the calculation of the outlet pressure boundary condition. A receptor–ligand model was used to simulate the particle binding probability. The results indicate that bigger particles have lower deposition fraction due to less chance of successful binding. Realistic unsteady flow significantly accelerates the binding activity over a wide range of particle sizes and also improves the particle deposition fraction in bifurcation regions when comparing with steady flow condition. Furthermore, surface imperfections and geometrical complexity coupled with the pulsatility effect can enhance fluid mixing and accordingly particle binding efficiency. The particle binding density at bifurcation regions increases with generation order and drug carriers are washed away faster in steady flow. Thus, when studying drug delivery mechanism in vitro and in vivo, it is important to take into account blood flow pulsatility in realistic geometry. Moreover, tissues close to bifurcations are more susceptible to deterioration due to higher uptake.

scholarly journals Computational and experimental investigation of particulate matter deposition in cerebral side aneurysms

2020 ◽  
Vol 17 (169) ◽  
pp. 20200510
Author(s):  
Mark Epshtein ◽  
Netanel Korin
Keyword(s):  
Experimental Investigation ◽  
Computational Model ◽  
Particle Deposition ◽  
Rational Design ◽  
Fluid Motion ◽  
Drug Carriers ◽  
Design And Optimization ◽  
Wide Range ◽  
Low Shear

Intracranial aneurysms frequently develop blood clots, plaque and inflammations, which are linked to enhanced particulate mass deposition. In this work, we propose a computational model for particulate deposition, that accounts for the influence of field forces, such as gravity and electrostatics, which produce an additional flux of particles perpendicular to the fluid motion and towards the wall. This field-mediated flux can significantly enhance particle deposition in low-shear environments, such as in aneurysm cavities. Experimental investigation of particle deposition patterns in in vitro models of side aneurysms, demonstrated the ability of the model to predict enhanced particle adhesion at these sites. Our results showed a significant influence of gravity and electrostatic forces (greater than 10%), indicating that the additional terms presented in our models may be necessary for modelling a wide range of physiological flow conditions and not only for ultra-low shear regions. Spatial differences between the computational model and the experimental results suggested that additional transport and fluidic mechanisms affect the deposition pattern within aneurysms. Taken together, the presented findings may enhance our understanding of pathological deposition processes at cardiovascular disease sites, and facilitate rational design and optimization of cardiovascular particulate drug carriers.

Gas Transport in Serpentine Microporous Tubes Under Steady and Pulsatile Blood Flow Conditions

1991 ◽  
Vol 113 (2) ◽  
pp. 223-229 ◽  
Author(s):  
Kazuo Tanishita ◽  
Masanobu Ujihira ◽  
Akihisa Watabe ◽  
Kunio Nakano ◽  
Peter D. Richardson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Transfer ◽  
Ex Vivo ◽  
Radius Of Curvature ◽  
Gas Transfer ◽  
Pulsatile Blood Flow ◽  
Flow Conditions ◽  
Wide Range ◽  
Exchange Unit

A serpentine gas exchange unit was built with cylindrical tubular microporous membranes featuring periodic arcs with a fixed curvature ratio (ratio of tube radius to radius of curvature) of 1/14 and circular angles between 30 and 360 deg. Oxygen transfer was measured under steady and pulsatile blood flow conditions in vitro and ex vivo to assess the design features which most effectively augment gas transfer. Under steady blood flow conditions, oxygen transfer increased with circular angles beyond 70 deg. Under pulsatile conditions, a wide range of geometrical and fluid mechanical parameters could be combined to enhance gas transfer performance, which eventually depended upon the secondary Reynolds number and the Womersley parameter.

scholarly journals Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

2019 ◽  
Author(s):  
Maria Camilla Operti ◽  
Yusuf Dölen ◽  
Jibbe Keulen ◽  
Eric A.W. van Dinther ◽  
Carl G. Figdor ◽  
...  
Keyword(s):  
Particle Size ◽  
Suppressor Cells ◽  
Drug Carriers ◽  
Production Method ◽  
Biological Evaluation ◽  
Particle Uptake ◽  
Wide Range ◽  
Formulation Parameters

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

scholarly journals Dendrimer-Functionalized Hybrid Materials Based on Silica as Novel Carriers of Bioactive Acids

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2660
Author(s):  
Mateusz Pawlaczyk ◽  
Grzegorz Schroeder
Keyword(s):  
Hybrid Materials ◽  
Materials Science ◽  
Freundlich Isotherm ◽  
Drug Carriers ◽  
Pamam Dendrimers ◽  
Silica Matrix ◽  
Support Surface ◽  
Wide Range ◽  
Percentage Release

One of the major goals in the materials science is the design and development of non-toxic, versatile, and efficient drug delivery systems. The study reported in this paper concerns the syntheses of poly(amidoamine) (PAMAM) dendrimers with tris(2-aminoethyl)amine as an amine core and different terminal amines, and their attachment to silica matrix. The obtained ethylenediamine (EDA), triethylenetetramine (TETA), tris(2-aminoethyl)amine (TREN) and 4,7,10-trioxa-1,13-tridecanediamine (TRI-OXA) dendrimers were introduced to the support surface via an epoxy linker, leading to a loading efficiency in the range of 0.054–0.113 mmol g−1, determined using elemental and thermogravimetric analyses. The materials exhibited high adsorption capacities towards the chosen model drugs: folic, salicylic and nicotinic acid. The investigated adsorption processes were found to follow the Freundlich isotherm model, with indication of the drugs’ structure influence on the binding efficiency. Drug-loaded hybrid materials were also described for in vitro drug release in three pH-different paraphysiological media. The highest percentage release was obtained in the tests performed at pH 2.0, ranging between 35.42 and 99.83%. Satisfactory results and the versatility of PAMAM dendrimers may lead to the application of such materials not only as drug carriers dedicated to a wide range of pharmaceutics, but also as analytical tools for pre-concentration and/or the determination of biocompound contamination in samples.

Fluid Dynamics Analysis by CT Imaging Technique of New Sorbent Cartridges for Extracorporeal Therapies

2019 ◽  
Vol 48 (1) ◽  
pp. 18-24
Author(s):  
Anna Lorenzin ◽  
Mauro Neri ◽  
Massimo de Cal ◽  
Giordano Pajarin ◽  
Giuseppe Mansi Montenegro ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Blood Flow ◽  
Pressure Drop ◽  
Flow Rate ◽  
Imaging Technique ◽  
Blood Purification ◽  
Ct Imaging ◽  
Flow Profile ◽  
In Vitro Test

Background: Recent innovations in biomaterials technology have led to the development of innovative sorbents adopted as adsorbing devices in the field of extracorporeal blood purification therapies. As removal mechanism, adsorption allows to remove specific molecules, selectively binding them to sorbent materials. In addition to the material properties, a quintessential aspect influencing device properties is blood flow distribution within the sorbent particles. Objectives: In order to adequately characterize the potential adsorbing properties for an effective blood purification therapy, an in vitro study assessing the fluid dynamics inside 3 new cartridges, HA130, HA230 and HA330 (Jafron, Zhuhai City, ­China) was conducted through CT imaging technique. ­Methods: The cartridges were placed in vertical position in the CT ­gantry. Dye solution was circulated through the cartridges at 250 mL/min, longitudinal sections, 0.5 cm thick, were recorded for 60 s. Furthermore, an in vitro test was conducted to build pressure drop profiles. Blood was circulated at a different flow rate, 100–400 mL/min, step 50 mL/min. Pre and post cartridges pressures were acquired and pressure drop calculated. Results: Sequential images demonstrated an excellent distribution of the flow inside the cartridges. Average flow velocity was 0.37 cm/s for the 3 cartridges. HA130 had a homogeneous flow profile along the entire length of the device; HA230 and HA330 showed minimal differences between central and peripheral regions. Pressure drop profiles resulted linear, increasing proportionally with blood flow rate and packing density. Conclusions: We may conclude that the structural and functional design of the studied cartridges is adequate for haemoperfusion with no channelling phenomena. This ensures maximum and optimal utilization of the sorbent contained in the devices.

scholarly journals Considerations for Numerical Modeling of the Pulmonary Circulation—A Review With a Focus on Pulmonary Hypertension

2013 ◽  
Vol 135 (6) ◽  
Author(s):  
V. O. Kheyfets ◽  
W. O'Dell ◽  
T. Smith ◽  
J. J. Reilly ◽  
E. A. Finol
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Blood Flow ◽  
Numerical Models ◽  
Academic Research ◽  
Basic Research ◽  
Wall Stress ◽  
Pulmonary Vasculature ◽  
Future Research ◽  
Wide Range

Both in academic research and in clinical settings, virtual simulation of the cardiovascular system can be used to rapidly assess complex multivariable interactions between blood vessels, blood flow, and the heart. Moreover, metrics that can only be predicted with computational simulations (e.g., mechanical wall stress, oscillatory shear index, etc.) can be used to assess disease progression, for presurgical planning, and for interventional outcomes. Because the pulmonary vasculature is susceptible to a wide range of pathologies that directly impact and are affected by the hemodynamics (e.g., pulmonary hypertension), the ability to develop numerical models of pulmonary blood flow can be invaluable to the clinical scientist. Pulmonary hypertension is a devastating disease that can directly benefit from computational hemodynamics when used for diagnosis and basic research. In the present work, we provide a clinical overview of pulmonary hypertension with a focus on the hemodynamics, current treatments, and their limitations. Even with a rich history in computational modeling of the human circulation, hemodynamics in the pulmonary vasculature remains largely unexplored. Thus, we review the tasks involved in developing a computational model of pulmonary blood flow, namely vasculature reconstruction, meshing, and boundary conditions. We also address how inconsistencies between models can result in drastically different flow solutions and suggest avenues for future research opportunities. In its current state, the interpretation of this modeling technology can be subjective in a research environment and impractical for clinical practice. Therefore, considerations must be taken into account to make modeling reliable and reproducible in a laboratory setting and amenable to the vascular clinic. Finally, we discuss relevant existing models and how they have been used to gain insight into cardiopulmonary physiology and pathology.

scholarly journals Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 590 ◽  
Author(s):  
Maria Camilla Operti ◽  
Yusuf Dölen ◽  
Jibbe Keulen ◽  
Eric A. W. van Dinther ◽  
Carl G. Figdor ◽  
...  
Keyword(s):  
Particle Size ◽  
Suppressor Cells ◽  
Drug Carriers ◽  
Production Method ◽  
Biological Evaluation ◽  
Particle Uptake ◽  
Wide Range ◽  
Formulation Parameters

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

500 An in vitro steady flow model of mitral regurgitation by three-dimensional Doppler

1999 ◽  
Vol 1 ◽  
pp. S86-S86
Author(s):  
R DESIMONE ◽  
G GLOMBITZA ◽  
C VAHL ◽  
H MEINZER ◽  
S HAGL
Keyword(s):  
Mitral Regurgitation ◽  
Steady Flow ◽  
Flow Model ◽  
Three Dimensional

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Activation ◽  
In Vivo Studies ◽  
Blood Flow Response ◽  
Flow Response

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

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