•Human skin layers and capillaries are considered as composite porous medium involving convection and diffusion of fluids.•Dynamic boundary conditions are employed to model skin layer growth.•New ...design with optimally spaced multiple drug heads is proposed to enhance transdermal drug diffusion. This arrangement reduce skin irritation associated with conventional patches.•An enhancement of 100% in diffusive flux from patch heads and a reduction of upto 50% in steady state approach time over the conventional patch were achieved by varying the effective area ratio.•Depending upon the effective area ratio chosen, two superior drug head configurations suggested were found to increase the average flux of the design further by 5% to 40%.
In this study, we propose an enhanced design of transdermal drug patch that offers better pharmacological efficacy and patient compliance than conventional designs that necessitate the entire skin under the patch to be in direct contact with the drug. This new design involves several periodically repeating portions of patched and unpatched areas, which creates a series of high local flux regions around the boundary between these patched and unpatched areas because of increased lateral spread of drug. Using numerical simulations of governing mass transfer equations for blood flow through trans-dermal regions modelled as a porous medium, the proposed design was found to be 100% more effective than the conventional one in terms of average flux from the drug head. A reduction of up to 50%, in the time required to reach steady state was also observed with the new design. Depending upon the effective area ratio chosen, the two superior drug head configurations suggested were found to be able to increase the average flux of the design further by 5% to 40%. The findings of the study provide a new approach by which one can design and fabricate transdermal patches that can accurately deliver any required dose without the use of a rate limiting membrane.
Study of non-Fourier energy transport is important in various biomedical applications, in the understanding of heat transfer in biological tissues. One such biomedical application that involves ...non-Fourier heat conduction is laser irradiation of the retina, where a high heat flux is typically applied for a short period of time. In the present study, retinal laser irradiation is analysed using the dual phase lag model for heat conduction. A simplified one-dimensional model of the human eye with seven layers is used in the simulation. The laser heating is modelled as a volumetric heat source and the respective magnitudes are calculated based on the absorptivities of the various layers. Apart from the temperature distribution, the damage distribution is also computed using the Arrhenius damage integral approach. The effect of the two phase lags τq and τT on the temperature and damage distributions are analysed. Small τT/τq ratios (⩽0.01) indicate a thermal wave like behaviour, which diminishes as the ratio increases (i.e. for τT/τq⩾0.1). The results are also compared with corresponding results from the Fourier model. Choroidal blood perfusion rate is found to have no significant effect on the unsteady temperature and damage distributions.
Abstract
We report an in vitro transient experimental study of the human eye to determine the effects of convection on the transport of drugs from the point of injection to the retinal surface ...through the fluid in the vitrectomized eye. The human eye is modeled as a glass orb of realistic proportions, and water and silicone oil mimic the vitreous fluid. In a series of experiments, the dye that is used to mimic the drug is injected at two different spots in the vitreous chamber, and its transport through the vitreous fluid mimic to the retinal surface is recorded under conditions of simple diffusion and convection‐assisted diffusion. The drug concentrations at two different spots on the retinal surface at different times are monitored. It is shown that the drug reaches all parts of the retinal surface much faster during convection‐assisted diffusion than during pure diffusion, irrespective of where it is injected in the cavity. In a snapshot, it is seen that the dye concentration reaches at the target central retinal pigmented epithelium spot in just 12 min (0.2 h) with convection‐assisted diffusion as against 12 h in pure diffusion. The steady‐state average drug concentration at the target retinal region is seen to be 56.25 times greater for the convection‐assisted drug transport than for the pure diffusion case. The results show that applying mild heat to the retinal surface by methods such as laser irradiation can induce convection‐based transport of the drug in the vitreous fluid. This method makes the drug available much faster at the target retinal region than drug transport by pure diffusion. The faster transport of the drug within the cavity can expedite the drug's effect and prevent drug loss due to delays.
Transscleral drug delivery is one of the methods of depositing drug in the posterior segment (comprising retina, choroid, sclera and macula) of the human eye, to treat diseases such as age related ...macular degeneration (AMD). In this study, the effect of choroidal blood flow on transscleral drug delivery to the retina is investigated using a porous medium model of the sclera and the choroid. A two-dimensional geometrical model of the human eye is constructed from available measurements and determination of physicochemical properties of the sclera and the choroid, such as their effective diffusivity D and porous medium permeability K. Position and time dependent concentrations of the drug in the sclera and the choroid are predicted and the relative magnitudes of the periocular, vitreous and circulation losses are compared for various blood flow velocities Ub. The simulations also predict the transient mean plasma concentration C¯ of the drug anecortave desacetate in the choroid and the effect of choroidal blood flow on the peak mean plasma concentration C¯max. Comparison of predicted C¯ with available experimental results is good.
Infants born with univentricular heart disease undergo Fontan surgery to establish separate systemic and pulmonary circulations. This surgery results in better blood circulation across a single ...ventricle that supplies oxygenated blood to the body and passively returns venous blood to the lungs through the total cavopulmonary connection (TCPC). Reducing the pressure drop across the TCPC during Fontan circulation helps in reducing the work load of univentricular heart, and various designs have been proposed for this purpose. The goal of this work is to analyze the effect of placing a porous insert at an appropriate position in the pulmonary artery, on the pressure drop across the TCPC. A 3D computational model of a total TCPC connection provided with a porous insert is developed and solved by finite volume method, under assumptions of steady, laminar, and Newtonian flows. The effects of the porous medium properties—porosity and permeability—across the connection, are analyzed. Compared to the no‐porous medium case, TCPC with the porous medium insert exhibits a maximum reduction of 27% in energy loss for the flow range studied. The porous medium used in TCPC connection lowers the energy dissipation by curtailing the flow recirculation zones across the connection. The influences of the diameter of the blood vessel, total cardiac output, and the thickness, permeability, and position of porous media on energy loss are analyzed. The criteria to select the porous medium properties and position for a given Fontan geometry are also determined.
Porous medium inserts placed in total cavo‐pulmonary connection during Fontan surgery are shown to lower the energy dissipation by curtailing the flow recirculation zones across the connection. The influences of the diameter of the blood vessel, total cardiac output, and the thickness, permeability, and position of porous media on energy loss are analyzed. The criteria to select the porous medium properties and position for a given Fontan geometry are also determined.
During laser-assisted photo-thermal therapy, the temperature of the heated tissue region must rise to the therapeutic value (e.g., 43°C) for complete ablation of the target cells. Large blood vessels ...(larger than 500 micron in diameter) at or near the irradiated tissues have a considerable impact on the transient temperature distribution in the tissue. In this study, the cooling effects of large blood vessels on temperature distribution in tissues during laser irradiation are predicted using finite element based simulation. A uniform flow is assumed at the entrance and three-dimensional conjugate heat transfer equations in the tissue region and the blood region are simultaneously solved for different vascular models. A volumetric heat source term based on Beer–Lambert law is introduced into the energy equation to account for laser heating. The heating pattern is taken to depend on the absorption and scattering coefficients of the tissue medium. Experiments are also conducted on tissue mimics in the presence and absence of simulated blood vessels to validate the numerical model. The coupled heat transfer between thermally significant blood vessels and their surrounding tissue for three different tissue-vascular networks are analyzed keeping the laser irradiation constant. A surface temperature map is obtained for different vascular models and for the bare tissue (without blood vessels). The transient temperature distribution is seen to differ according to the nature of the vascular network, blood vessel size, flow rate, laser spot size, laser power and tissue blood perfusion rate. The simulations suggest that the blood flow through large blood vessels in the vicinity of the photothermally heated tissue can lead to inefficient heating of the target.
•We address the cooling effects of LBV on tissues during photo-thermal heating.•Experiments are performed on tissue mimic to validate the numerical simulation.•Different tissue vascular network gives different thermal history.•A non-invasive IR imaging technique is used instead of localized thermocouples.•A parametric study to quantify the effect of laser specification and blood flow.
The success of laser hyperthermia in the treatment of cancer depends on the extent of heat diffusion to the cancerous tissue. Understanding and optimising hyperthermia treatment requires accurate ...measurement and control of temperature distribution. This paper reports experimental and theoretical results of surface temperature distribution and thermal lagging effect in tissue-mimics during laser irradiation. Experiments are conducted on bio-tissue mimics embedded with and without gold nanostructures irradiated by a continuous wave diode-pumped solid state laser having wavelength of 1064 nm. The experimental results of surface temperature distribution are compared with the computational prediction, obtained by solving numerically the Pennes bio-heat transfer based on classical Fourier model and on the dual phase lag model. Based on the multiple scattering phenomenon a new model for the laser attenuation in tissues is proposed. It compares well with the experimental data. In addition, the qualitative nature of damage to bio-tissue upon laser irradiation has been examined experimentally using atomic force microscopy to demonstrate the denaturation potential of the surface temperature, when gold nanostructures are used to mitigate temperature rise.
•The present work measured the surface and axial temperature distribution in bio-tissue mimics during NIR laser irradiation.•A model for laser attenuation in tissues, based on multiple scattering theory has been proposed.•The present model claims that the values of the phase lag times for τq and τT should be 2 to 8 s and 0.045 s respectively.•The thermal denaturation of collagen with and without presence of gold nanostructures upon laser irradiation was studied experimentally using atomic force microscopy.•The non-Fourier nature of heat conduction is apparent in heterogeneous materials like biological tissues.
A validated two-dimensional computational model of the human eye solving the discretized form of the bio-heat transfer equation using finite volume formulation has been developed. Using the model, ...the transient temperature evolution and associated thermal effects in various regions of the human eye subjected to laser radiation during retinopathy are investigated. It is shown that the transient evolution of the retinal temperature during laser heating could reach values higher than that required for irreversible cell damage. This is because the time scale for spatial diffusion of heat towards the choroid, containing blood vessels for cooling, is much larger than that of the actual laser surgical process (100
ms). This excess temperature could cause cell damage to the adjoining retinal region due to heat diffusion. Based on the simulation results, a method is proposed to maintain the retinal pigmented epithelium (RPE) temperature close to the required 60
°C by pulsating the laser source between suitable maximum and minimum heat flux values.
Purpose
– The large blood vessels (LBV) would act as a heat sink and hence play a significant role during photo-thermal therapy. Gold nanoshell was considered as a high-heat absorbing agent in ...photo-thermal heating to reduce the cooling effect of LBV. The heat sink effect of LBV results in insignificant irreversible tissue thermal damage. The paper aims to discuss these issues.
Design/methodology/approach
– In this paper, the thermal history of tissue embedded with LBV during photo-thermal heating were calculated using finite element-based simulation technique. A volumetric laser source term based on modified Beer-Lambert law was introduced to model laser heating. The numerically predicted temperature drop was validated against that of previously performed experiments by the authors on tissue mimic embedded with simulated blood vessels. In the later part of the study, Arrhenius equation was coupled with the energy equation to investigate and report the irreversible thermal damage to the bio-tissues.
Findings
– The results obtained conclude that tissue with different orientation of blood vessels results in different thermal response at the tissue surface. Gold nanoshells were introduced into the laser irradiated tissue to overcome the cooling effect of LBV during plasmonic photo-thermal heating. The effect of size and concentration of nanoparticles on tissue heating were analyzed. The predicted damage parameter was much lower in case of tissue embedded with blood vessel than that predicted in case of bare tissue, which results in incomplete tissue necrosis. Finally, the effects of laser specification, blood vessel specification and blood perfusion on the tissue thermal damage were examined.
Originality/value
– The conjugate energy equations in conjunction with Arrhenius equation were solved numerically to predict the tissue irreversible damage embedded with LBV.
