Coupled gel spreading and diffusive transport models describing microbicidal drug delivery.

Gels are a drug delivery platform that is being evaluated for application of active pharmaceutical ingredients, termed microbicides, that act topically against vaginal and rectal mucosal infection by sexually transmitted HIV. Despite success in one Phase IIb trial of a vaginal gel delivering tenofovir, problems of user adherence to designed gel application scheduling have compromised results in two other trials. The microbicides field is responding to this dilemma by expanding behavioral analysis of the determinants of adherence while simultaneously improving the pharmacological, biochemical, and biophysical analyses of the determinants of microbicide drug delivery. The intent is to combine results of these two complementary perspectives on microbicide performance and epidemiological success to create an improved product design paradigm. Central to both user sensory perceptions and preferences, key factors that underlie adherence, and to vaginal gel mucosal drug delivery, that underlies anti-HIV efficacy, are gel properties (e.g. rheology) and volume. The specific engineering problem to be solved here is to develop a model for how gel rheology and volume, interacting with loaded drug concentration, govern the transport of the microbicide drug tenofovir into the vaginal mucosa to its stromal layer. These are factors that can be controlled in microbicide gel design. The analysis here builds upon our current understanding of vaginal gel deployment and drug delivery, incorporating key features of the gel's environment, the vaginal canal, fluid production and subsequent gel dilution, and vaginal wall elasticity. These have not previously been included in the modeling of drug delivery. We consider the microbicide drug tenofovir, which is the drug most completely studied for gels: in vitro, in animal studies in vivo, and in human clinical trials with both vaginal or rectal gel application. Our goal is to contribute to improved biophysical and pharmacological understanding of gel functionality, providing a computational tool that can be used in future vaginal microbicide gel design.

Transient spreading and swelling behavior of a gel deploying an anti-HIV topical microbicide.

Drug delivery of topical microbicidal molecules against HIV offers promise as a modality to prevent sexual transmission of the virus. Success of any microbicide product depends, in an interactive way, upon its drug (the microbicide active pharmaceutical ingredient, API) and its delivery system (e.g. a gel, film or intravaginal ring). There is a widespread agreement that more effective drug delivery vehicles, as well as better APIs, must be developed to improve the efficacy of microbicide products. Non-Newtonian gels are primary microbicide vehicles, but those to date have been created with limited understanding of how their properties govern their spreading and retention in the vagina, which, in turn, govern successful drug delivery. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a gel and the vaginal environment. We address several critical components of this complex process, including: elastohydrodynamic flow of the bolus of a non-Newtonian fluid; and mass transfer due to inhomogeneous dilution of the gel by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface). Local dilution of gel alters local rheological properties. We evaluated this experimentally, delin-eating the way that constitutive parameters of a shear-thinning gel are modified by dilution. We supplement the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the gel bolus. This is a physicochemically complex phenomenon that is not well understood. We implement a boundary flux model based upon the elevated hydrodynamic pressures in the cells. Results show that this model produces fluxes that lie within the range of mean values that have been reported. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.

Irreversibility analysis of an unsteady micropolar CNT-blood nanofluid flow through a squeezing channel with activation energy-Application in drug delivery.

BACKGROUND AND OBJECTIVE: Due to the low toxicity, unique physiochemical properties, and appropriate surface modifications, Carbon Nanotubes (CNTs) are used as target carriers in drug delivery systems. In the present problem, we have considered both single-walled and multi-walled CNTs to study the impact of irreversibility on the micropolar nanofluid flow through a squeezing channel with the base fluid blood. The blood is considered a micropolar fluid in the presence of different blood cells and their rotational nature. Further, blood is influenced by the external magnetic field parallel to the microrotation along with viscous and Joule dissipations. METHOD: Highly coupled and nonlinear partial differential equations are solved with Homotopy Analysis Method (HAM) after simplified equations using similarity transformation. Further, we have concluded the minimum squared residual errors to show the method's accuracy. A comparison made with the existing literature and shows a good agreement. RESULTS: The angular velocity of the fluid particles is enhanced by increasing the squeezing number. In the case of the squeezing, volume fraction has improved the viscous drag and is found high for MWCNT embedded nanofluid. The heat transfer rate is higher for the MWCNT embedded nanofluid than the SWCNT embedded nanofluid. A descent found in entropy generation boosts up with the Brinkman parameter while opposite phenomena appear for radiation and Hartman number and vortex viscosity. Both Bejan number and entropy generation profiles are restricted with an increase in vortex viscosity. CONCLUSION: SWCNTs are showed to be more effective and efficient than the MWCNTs in elevating velocity, temperature and irreversibility of the system. Outcomes of this problem will help to understand the implementation of the drug carrier and irreversibility phenomena during drug delivery.

Electroosmotic modulated unsteady squeezing flow with temperature-dependent thermal conductivity, electric and magnetic field effects.

Modern lubrication systems are increasingly deploying smart (functional) materials. These respond to various external stimuli including electrical and magnetic fields, acoustics, light etc. Motivated by such developments, in the present article unsteady electro-magnetohydrodynamics squeezing flow and heat transfer in a smart ionic viscous fluid intercalated between parallel plates with zeta potential effects is examined. The proposed mathematical model of problem is formulated as a system of partial differential equations (continuity, momenta and energy). Viscous dissipation and variable thermal conductivity effects are included. Axial electrical distribution is also addressed. The governing equations are converted into ordinary differential equations via similarity transformations and then solved numerically with MATLAB software. The transport phenomena are scrutinized for both when the plates move apart or when they approach each other. Also, the impact of different parameters such squeezing number, variable thermal conductivity parameter, Prandtl number, Hartmann number, Eckert number, zeta potential parameter, electric field parameter and electroosmosis parameter on the axial velocity and fluid temperature are analysed. For varied intensities of applied plate motion, the electro-viscous effects derived from electric double-capacity flow field distortions are thoroughly studied. It has been shown that the results from the current model differ significantly from those achieved by using a standard Poisson-Boltzmann equation model. Axial velocity acceleration is induced with negative squeeze number (plates approaching,S< 0) in comparison to that of positive squeeze number (plates separating,S> 0). Velocity enhances with increasing electroosmosis parameter and zeta potential parameter. With rising values of zeta potential and electroosmosis parameter, there is a decrease in temperatures forUe> 0 for both approaching i.e. squeezing plates (S< 0) and separating (S> 0) cases. The simulations provide novel insights into smart squeezing lubrication with thermal effects and also a solid benchmark for further computational fluid dynamics investigations.

Theoretical analysis of unsteady squeezing nanofluid flow with physical properties.

Theoretical analysis of physical characteristics of unsteady, squeezing nanofluid flow is studied. The flow of nanofluid between two plates that placed parallel in a rotating system by keeping the variable physical properties: viscosity and thermal conductivity. It is analyzed by using Navier Stokes Equation, Energy Equation and Concentration equation. The prominent equations are transformed by virtue of suitable similarity transformation. Nanofluid model includes the important effects of Thermophoresis and Brownian motion. For analysis graphical results are drawn for verity parameters of our interest i.e., Injection parameter, Squeezing number, Prandtle number and Schmidt number are investigated for the Velocity field, Temperature variation and Concentration profile numerically. The findings underline that the parameter of skin friction increases when the Squeezing Reynolds number, Injection parameter and Prandtle number increases. However, it shows inverse relationship with Schmidt number and Rotation parameter. Furthermore, direct relationship of Nusselt number with injection parameter and Reynolds number is observed while its relation with Schmidt number, Rotation parameter, Brownian parameter and Thermophoretic parameter shows an opposite trend. The results are thus obtained through Parametric Continuation Method (PCM) which is further validated through BVP4c. Moreover, the results are tabulated and set forth for comparison of findings through PCM and BVP4c which shows that the obtained results correspond to each other.

Entropy Generation and Statistical Analysis of MHD Hybrid Nanofluid Unsteady Squeezing Flow between Two Parallel Rotating Plates with Activation Energy.

Squeezing flow is a flow where the material is squeezed out or disfigured within two parallel plates. Such flow is beneficial in various fields, for instance, in welding engineering and rheometry. The current study investigates the squeezing flow of a hybrid nanofluid (propylene glycol-water mixture combined with paraffin wax-sand) between two parallel plates with activation energy and entropy generation. The governing equations are converted into ordinary differential equations using appropriate similarity transformations. The shooting strategy (combined with Runge-Kutta fourth order method) is applied to solve these transformed equations. The results of the conducted parametric study are explained and revealed in graphs. This study uses a statistical tool (correlation coefficient) to illustrate the impact of the relevant parameters on the engineering parameters of interest, such as the surface friction factor at both plates. This study concludes that the squeezing number intensifies the velocity profiles, and the rotating parameter decreases the fluid velocity. In addition, the magnetic field, rotation parameter, and nanoparticle volumetric parameter have a strong negative relationship with the friction factor at the lower plate. Furthermore, heat source has a strong negative relationship with heat transfer rate near the lower plate, and a strong positive correlation with the same phenomena near the upper plate. In conclusion, the current study reveals that the entropy generation is increased with the Brinkman number and reduced with the squeezing parameter. Moreover, the results of the current study verify and show a decent agreement with the data from earlier published research outcomes.

Evaluation of entropy generation in cubic autocatalytic unsteady squeezing flow of nanofluid between two parallel plates.

BACKGROUND: Nanomaterials have advanced behaviors that make them possibly beneficial in various applications in mass and heat transports such as engine cooling, pharmaceutical processes, fuel cells, engine cooling and domestic refrigerator etc. Therefore here we deliberated the entropy generation in unsteady magnetohydrodynamic squeezing flow of viscous nanomaterials between two parallel plates. The upper plate is squeezing towards lower plate. The lower plate exhibits porous character. Energy attributes are discussed through heat flux, dissipation and Joule heating. Furthermore the irreversibility analysis with cubic autocatalysis chemical reaction is also accounted. METHODS: Nonlinear differential systems are converted to ordinary differential system by transformations. For convergent series solution the given system are solved by homotopy analysis method (HAM). RESULTS: Characteristics of various interesting variables on velocity, Bejan number, concentration, entropy optimization and temperature are deliberated through graphs. Gradient of velocity (Cfx) and Nusselt number (Nux) are numerically computed against various physical variables. Entropy generation and Bejan number both quantitatively enhance versus radiation parameter. For larger squeezing parameter the velocity and temperature field are increased. CONCLUSIONS: The obtained results show that for larger squeezing parameter the velocity field boosts up. Velocity have opposite impact For larger magnetic and porosity parameters. Temperature is decreased for higher values of radiation parameter and Prandtl number. Temperature and concentration have same outcome for thermophoresis parameter. Entropy generation and Bejan number both quantitatively enhance versus radiation parameter, while reverse is hold for Brinkman number.

The Self-Enforcing Starch-Gluten System-Strain-Dependent Effects of Yeast Metabolites on the Polymeric Matrix.

The rheological behaviour of dough during the breadmaking process is strongly affected by the accumulation of yeast metabolites in the dough matrix. The impact of metabolites in yeasted dough-like concentrations on the rheology of dough has not been characterised yet for process-relevant deformation types and strain rates, nor has the effect of metabolites on strain hardening behaviour of dough been analysed. We used fundamental shear and elongational rheometry to study the impact of fermentation on the dough microstructure and functionality. Evaluating the influence of the main metabolites, the strongest impact was found for the presence of expanding gas cells due to the accumulation of the yeast metabolite CO2, which was shown to have a destabilising impact on the surrounding dough matrix. Throughout the fermentation process, the polymeric and entangled gluten microstructure was found to be degraded (-37.6% average vessel length, +37.5% end point rate). These microstructural changes were successfully linked to the changing rheological behaviour towards a highly mobile polymer system. An accelerated strain hardening behaviour (+32.5% SHI for yeasted dough) was promoted by the pre-extension of the gluten strands within the lamella around the gas cells. Further, a strain rate dependency was shown, as a lower strain hardening index was observed for slow extension processes. Fast extension seemed to influence the disruption of sterically interacting fragments, leading to entanglements and hindered extensibility.

Impacts of magnetic field and thermal radiation on squeezing flow and heat transfer of third grade nanofluid between two disks embedded in a porous medium.

In this present study, the impacts of magnetic field and thermal radiation on squeezing flow and heat transfer of third grade nanofluid between two disks embedded in a porous medium with temperature jump boundary conditions is analyzed using differential transformation method. The results of the approximate analytical solutions are verified using a fifth-order Runge-Kutta Fehlberg method (Cash-Karp Runge-Kutta) coupled with shooting method. From the analysis, the results of the two methods show excellent agreements. Also, the parametric studies using the approximate analytical solutions show that for a suction parameter greater than zero, the radial velocity of the lower disc increases while that of the upper disc decreases as a result of a corresponding increase in the viscosity of the fluid from the lower squeezing disc to the upper disc. For an increasing magnetic field parameter, the radial velocity of the lower disc decreases while that of the upper disc increases. As the third grade fluid parameter increases, there is a reduction in the fluid viscosity thereby increasing resistance between the fluid molecules. Also, it is found that as the radiation parameter increases, rate of heat transfer to the third grade fluid increases. There is a recorded decrease in the fluid temperature profile as the Prandtl number increases due to decrease in the thermal diffusivity of the third grade fluid. The agreement of the results of the present study and the experimental work shows the validation of the models used in this work to study the flow behaviour of the fluid. It is envisaged that the present work will increase the understanding of the flow behaviour of third grade nanofluid and heat transfer processes as evident in coal slurries, polymer solutions, textiles, ceramics, catalytic reactors, oil recovery applications etc.