scholarly journals Macroscopic Modeling of In Vivo Drug Transport in Electroporated Tissue

2016 ◽  
Vol 138 (3) ◽  
Author(s):  
Bradley Boyd ◽  
Sid Becker

This study develops a macroscopic model of mass transport in electroporated biological tissue in order to predict the cellular drug uptake. The change in the macroscopic mass transport coefficient is related to the increase in electrical conductivity resulting from the applied electric field. Additionally, the model considers the influences of both irreversible electroporation (IRE) and the transient resealing of the cell membrane associated with reversible electroporation. Two case studies are conducted to illustrate the applicability of this model by comparing transport associated with two electrode arrangements: side-by-side arrangement and the clamp arrangement. The results show increased drug transmission to viable cells is possible using the clamp arrangement due to the more uniform electric field.

Author(s):  
Maximilian S. Mesquita ◽  
Marcelo J. S. de Lemos

In this work, results for a macroscopic mass transport model are presented for a parallel plate channel filled with a fluid saturated heterogeneous porous medium. The numerical methodology herein employed is based on the control volume approach. Turbulence is assumed to exist within the fluid phase. High and low Reynolds k-e models were used to model such non-linear effects. The flow equations at the pore-scale were numerically solved using the SIMPLE method applied to a non-orthogonal boundary-fitted coordinate system. Integrated mass fraction results were compiled leading to correlations for the mass dispersion coefficients in the x and y directions. Application of the macroscopic model using the proposed correlations showed the role of dispersion mechanism in the overall transport in porous media.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 139 ◽  
Author(s):  
Yvonne Arnold ◽  
Julien Thorens ◽  
Stéphane Bernard ◽  
Yogeshvar Kalia

Drug absorption across viable porcine intestines was investigated using an Ussing chamber system. The apparent permeability coefficients, Papp,pig, were compared to the permeability coefficients determined in humans in vivo, Peff,human. Eleven drugs from the different Biopharmaceutical Classification System (BCS) categories absorbed by passive diffusion with published Peff,human values were used to test the system. The initial experiments measured Papp,pig for each drug after application in a Krebs–Bicarbonate Ringer (KBR) buffer and in biorelevant media FaSSIF V2 and FeSSIF V2, mimicking fasted and fed states. Strong sigmoidal correlations were observed between Peff,human and Papp,pig. Differences in the segmental Papp,pig of antipyrine, cimetidine and metoprolol confirmed the discrimination between drug uptake in the duodenum, jejunum and ileum (and colon); the results were in good agreement with human data in vivo. The presence of the P-gp inhibitor verapamil significantly increased Papp,pig across the ileum of the P-gp substrates cimetidine and ranitidine (p < 0.05). Clotrimazole, a potent CYP3A4 inhibitor, significantly increased Papp,pig of the CYP3A4 substrates midazolam, verapamil and tamoxifen and significantly decreased the formation of their main metabolites. In conclusion, the results showed that this is a robust technique to predict passive drug permeability under fasted and fed states, to identify regional differences in drug permeability and to demonstrate the activity of P-gp and CYP3A4.


Author(s):  
Mohamed R. Abdelaal ◽  
Milind A. Jog

The effect of viscosity ratio on the electric-field-driven enhancement of heat/mass transfer to a spherical liquid drop of one dielectric fluid from another immiscible dielectric fluid is computationally investigated in this paper. The flow field is considered to be in the Stokes regime and the energy (species) conservation equations in the continuous phase are solved numerically using a fully implicit finite volume method. Results for flow outside the drop, transient temperature distributions, Nusselt number variations, and heat/mass transfer enhancement are presented for Peclet numbers varying from 10 to 500, dimensionless electric field frequency from 50 to 1000, and the ratio of viscosity of the continuous to the dispersed phase varying from 0.1 to 50. Steady and non-uniform unsteady electric fields are considered. The computational simulations show that when viscosity of the drop is lower than the viscosity of the surrounding fluid, a steady uniform electric field is more effective in enhancement of heat/mass transport compared to a non-uniform time periodic electric field. Conversely, when the continuous phase is less viscous than the drop, the non-uniform time periodic electric field provides improved heat/mass transport than the steady uniform electric field.


2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Mokhamad Tirono ◽  
Suhariningsih

Sterilization using high-intensity electric fields is detrimental to health if safety is inadequate, so it is necessary to study the possibility of sterilization using low-intensity electric fields. This study aims to determine the lowest electric field intensity and treatment time to deactivate the bacteria that make up the biofilms and explain the mechanism of inactivation. The study samples were biofilms from the bacteria Pseudomonas aeruginosa and Staphylococcus epidermidis grown on the catheter. The modeling formula was developed from the Pockels effect and the Weibull distribution with the treatment using a square pulse-shaped electric field with a pulse width of 50 μs and an intensity of 2.0-4.0 kV/ cm. The results showed that the threshold for irreversible electroporation of both samples occurred in the treatment using an electric field with an intensity of 3.5 kV/cm and 3.75 kV/ cm, respectively, where the size and type of Gram of bacteria influenced. Moreover, the time of the treatment had an effect when irreversible electroporation occurred. However, when there was reversible electroporation, the effect of treatment time on the reduction in the number of bacteria was not significant. Also, changes in conductivity affected the reduction in the number of bacteria when reversible electroporation occurred.


2014 ◽  
Vol 136 (9) ◽  
Author(s):  
Mary Phillips

Nonthermal irreversible electroporation (NTIRE) is an ablation modality that utilizes microsecond electric fields to produce nanoscale defects in the cell membrane. This results in selective cell death while preserving all other molecules, including the extracellular matrix. Here, finite element analysis and experimental results are utilized to examine the effect of NTIRE on the small intestine due to concern over collateral damage to this organ during NTIRE treatment of abdominal cancers. During previous studies, the electrical treatment parameters were chosen based on a simplified homogeneous tissue model. The small intestine, however, has very distinct layers, and a more realistic model is needed to further develop this technology for precise clinical applications. This study uses a two-dimensional finite element solution of the Laplace and heat conduction equations to investigate how small intestine heterogeneities affect the electric field and temperature distribution. Experimental results obtained by applying NTIRE to the rat small intestine in vivo support the heterogeneous effect of NTIRE on the tissue. The numerical modeling indicates that the electroporation parameters chosen for this study avoid thermal damage to the tissue. This is supported by histology obtained from the in vivo study, which showed preservation of extracellular structures. The finite element model also indicates that the heterogeneous structure of the small intestine has a significant effect on the electric field and volume of cell ablation during electroporation and could have a large impact on the extent of treatment. The heterogeneous nature of the tissue should be accounted for in clinical treatment planning.


1997 ◽  
Vol 117 (11) ◽  
pp. 1109-1114
Author(s):  
Yoshiyuki Suda ◽  
Kenji Mutoh ◽  
Yosuke Sakai ◽  
Kiyotaka Matsuura ◽  
Norio Homma

2008 ◽  
Vol 128 (12) ◽  
pp. 1445-1451
Author(s):  
Takanori Yasuoka ◽  
Tomohiro Kato ◽  
Katsumi Kato ◽  
Hitoshi Okubo

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