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Objective: To manage the increasing burden of skin cancer cases globally and to replace conventional invasive treatments and their side effects, the present study is aimed to develop a transfersomal herbal gel of Green Tea Catechins (GTC) extracted from indigenous green tea and evaluate it for in vivo management of skin cancer in an experimental animal model. Methods: GTC-loaded transfersomes (GTCTF) were prepared by the thin-film hydration method. After optimizing the GTCTFs using the Box-Behnken design, they were characterized for zeta potential, structure, in vitro drug release, and in vitro skin permeation. Carbopol 940 gel was developed for the topical delivery of GTCTF and characterized for pH, viscosity, spreadability and in vitro skin permeation. In vitro MTT assay and in vivo chemopreventive and anticancer efficacy of the GTCTF gel were evaluated in mice. Results: The GTCTF has shown a particle size of 151.4±1.9 nm, entrapment efficiency of 68.25±0.06 %, and drug loading of 10.41±0.02 %. The in vitro MTT assay in B16F10 melanoma cell lines showed promising anticancer efficacy of the GTCTF. GTCTF gel was found suitable for topical delivery with favorable pH, viscosity, spreadability, and permeability and effective in preventing and curing skin cancer in mice, with a significant reduction of tissue biochemical parameters like TNF-α, IL-1β, and IL-6. Conclusion: Collectively, successful prevention and curing of the induced skin cancer in the experimental animal model by the GTCTF gel have established a novel herbal nanomedicine approach for the management of skin cancer.

The overcomplicated and elusive pathophysiology with unclear etiology, have been the main driving force of the medical scientists all over the world to develop a predictive, reliable, robust and reproducible simulation model of arthritis. This review highlights the osteoarthritis and rheumatoid arthritis with distinct conditions pertaining to each type of disease. The advances in various in vitro and in vivo experimental models of osteoarthritis and rheumatoid arthritis have been presented along with their pros and cons for antiarthritic drug discovery and formulation development. Additionally, the ethical issues to be considered while selecting animal models and handling them have been covered briefly. The current status quo on clinical trials of antiarthritic therapeutic interventions has also been covered.

Numerous studies suggest that disturbed shear, causing endothelium dysfunction, can be related to neighboring vortex structures. With this motivation, this study presents a methodology to characterize the vortex structures. Precisely, we use mapping and characterization of vortex structures' changes to relate it with the hemodynamic indicators of disturbed shear. Topological features of vortex core lines (VCLs) are used to quantify the changes in vortex structures. We use the Sujudi-Haimes algorithm to extract the VCLs from the flow simulation results. The idea of relating vortex structures with disturbed shear is demonstrated for cerebral arteries with aneurysms virtually treated by inserting foam in the sac. To get physiologically realistic flow fields, we simulate blood flow in two patient-specific geometries before and after foam insertion, with realistic velocity waveform imposed at the inlet, using the Carreau-Yashuda model to mimic the shear-thinning behavior. With homogenous porous medium assumption, flow through the foam is modeled using the Forcheimmer-Brinkmann extended Darcy model. Results show that foam insertion increases the number of VCLs in the parent lumen. The average length of VCL increases by 168.9% and 55.6% in both geometries. For both geometries under consideration, results demonstrate that the region with increased disturbed shear lies in the same arterial segment exhibiting an increase in the number of oblique VCLs. Based on the findings, we conjecture that an increase in oblique VCLs is related to increased disturbed shear at the neighboring portion of the arterial wall., 36 pages, 10 figures, 3 tables, submitted to Physical and Engineering Sciences in Medicine

Biodegradable polymers are the sustainable alternative to substitute the non-degradable synthetic plastics. The biopolymers and/ or bio-based polymers such as chitosan, starch, poly (lactic acid), ...

Purpose This paper aims to present the implementation of a multi-layer radiation propagation model in simulations of multi-phase flow and heat transfer, for a dissociating methane hydrate reservoir subjected to microwave heating. Design/methodology/approach To model the induced heterogeneity due to dissociation of hydrates in the reservoir, a multiple homogeneous layer approach, used in food processes modelling, is suggested. The multi-layer model is incorporated in an in-house, multi-phase, multi-component hydrate dissociation simulator based on the finite volume method. The modified simulator is validated with standard experimental results in the literature and subsequently applied to a hydrate reservoir to study the effect of water content and sand dielectric nature on radiation propagation and hydrate dissociation. Findings The comparison of the multi-layer model with experimental results show a maximum difference in temperature estimation to be less than 2.5 K. For reservoir scale simulations, three homogeneous layers are observed to be sufficient to model the induced heterogeneity. There is a significant contribution of dielectric properties of sediments and water content of the reservoir in microwave radiation attenuation and overall hydrate dissociation. A high saturation reservoir may not always provide high gas recovery by dissociation of hydrates in the case of microwave heating. Originality/value The multi-layer approach to model microwave radiation propagation is introduced and tested for the first time in dissociating hydrate reservoirs. The multi-layer model provides better control over reservoir heterogeneity and interface conditions compared to existing homogeneous models.

Objective: Curcumin presents poor topical bioavailability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of psoriasis. The present study reports the utilization of lipid-polymer hybrid nanoparticles (LPHNPs) for the topical delivery of curcumin which can be a potential approach for mitigating psoriasis. Methods: Curcumin-loaded LPHNPs were prepared by the emulsification solvent evaporation method and characterized. The optimized Curcumin-loaded LPHNPs (DLN-3) were further incorporated into 2% Carbopol 940 gels and evaluated for its therapeutic efficacy in the Imiquimod (IMQ)-induced psoriasis rat model. Results: The average particle size, polydispersity index, zeta potential, drug entrapment and loading efficiency for DLN-3 were found to be 200.9 nm, 0.342,-28.3 mV, 87.40±0.99% and 4.57±0.04%, respectively. FT-IR, DSC and XRD studies confirmed that all the components used for the formulation are compatible with each other, whereas SEM and TEM analysis affirmed the spherical shape of LPHNPs with a smooth surface. The in vitro drug release studies suggest that curcumin was released from the LPHNPs in a sustained manner over a period of 24 h via super case II transport mechanism. Results of in vitro skin permeation study revealed that 38.39±2.67% of curcumin permeated at 12 h across excised pig ear skin with a permeation flux of 18.74±3.59 µg/cm2/h. Further, in vivo evaluation and histopathological studies demonstrated that NLHG-1 hydrogels showed better therapeutic efficacy against the psoriatic skin lesions than the standard marketed gels. Conclusion: These results suggest that the developed LPHNPs have a superior ability to improve the skin penetration or accumulation of DLN-3 within psoriatic skin and offer a potential delivery system for the management of psoriasis.

Hydrate reservoirs present numerous challenges due to their occurrence in ultra-deep regions, presence of mud-layers, unconfined boundaries, and complex morphological heterogeneities. Individual ef...

This study proposes the use of artificial neural network (ANN) based surrogate framework along with simulated annealing (SA) approach to inversely estimate the optimum values of heat source control...

Bileaflet mechanical heart valves (BMHV) are widely implanted to replace diseased heart valves. Despite many improvements in design, these valves still suffer from various complications, such as valve dysfunction, tissue overgrowth, hemolysis, and thromboembolism. Thrombosis and thromboembolism are believed to be initiated by platelet activation due to contact with foreign surfaces and nonphysiological flow patterns. The implantation of the valve causes nonphysiological patterns of vortex shedding behind the leaflets. This study signifies the importance of vorticity in platelet activation and aggregation in BMHV implants. A two-phase model with the first Eulerian phase for blood and the second discrete phase for platelets is used here. The generalized cross model of viscosity has been used to simulate the non-Newtonian viscosity of blood. A fluid–structure-interaction model has been used to simulate the motion of leaflets. This study has also estimated the platelet activation state (PAS), which is the mathematical estimation of the degree of activation of platelets due to flow-induced shear stresses that cause thrombus formation. The regions in the fluid domain with a higher vorticity field have been found to contain platelets with relatively higher PAS than regions with relatively lower vorticity fields. Also, this study has quantitatively reported the effect of vorticity on platelet aggregation. Platelet densities in fluid areas with higher vorticity are higher than densities in fluid areas with lower vorticity, indicating that highly activated platelets aggregate in areas with stronger vorticity.

The present work investigates the complexities of unsteady targeted particle delivery in tortuous cerebral artery with three-dimensional twists and bends. Blood flow is modeled to mimic realistic pulsatile flow conditions along with its shear thinning behavior. One-way coupling is used to model particle flow. Dynamic particle release map (DPRM) for the targeted site, saccular aneurysm sac present in the artery, is determined on a chosen lumen cross section. Temporal variations in DPRM are analyzed and preferable catheter injection position and particle release pattern are recommended for minimum systemic toxicity.

Streptomyces is genetically and functionally diverse genus known to produce a wide array of phenolics and flavonoids with significant biotechnological applications. 52 isolates belonging to 26 species of Streptomyces collected from Meghalaya, India were analyzed for their genetic diversity using BOX-PCR. Significant inter- and intra- generic diversity was observed among the Streptomyces isolates especially those belonging to S. cacaoi, S. lavendulae, S. olivochromogenes, S. aureus, S. flavovirens. During bioactivity screening of the isolates, S. rectiviolaceus MJM72 recorded the highest DPPH activity (77.13 ± 0.91%) whereas S. antimycoticus MSCA162 showed excellent ABTS radical scavenging activity (99.65 ± 0.41%). On the other hand, S. novaecaesareae MJM58 had the highest (756.4 ± 7.38 μg GAE g

Fluid flows characterized by density variations have been studied using the schlieren-particle image velocimetry (PIV) system. The knife-edge location plays a crucial role in determining the system’s sensitivity, which significantly affects the accuracy of the measured quantities. Further, the optimum knife-edge position and the correct combination of image recording speed and interrogation window size are desirable for achieving the most accurate and reliable results. The present paper discusses the above issues on the measured quantities, such as temperature field, local Nusselt number distribution along the conducting walls, average Nusselt number, and velocity field. The experiment is performed to investigate laminar and steady natural convective flow in a water-enclosed cubic cavity with a left hot wall and a right cold wall. The analysis is undertaken for various knife-edge positions (0–90%), different image time separation varying (20–200 ms,) and interrogation window size using two passes varying from W1 = 32 pixels, W2 = 16 pixels to W1 = 128 pixels, W2 = 64 pixels. The results are presented for two distinct Rayleigh number, 1 × 108 and 3 × 108. Three-dimensional simulations have been carried out to check the fidelity of the experiment for Ra = 1 × 108. A high dynamic range of temperature is obtained for the range of knife-edge position in 50–65% while a high-velocity range is realized for knife-edge cutoff of 65% and combination of image time separation of Δt = 100 ms and interrogation window size with two passes of W1 = 64 pixels followed by W2 = 32 pixels.

The present research investigates the mass transfer processes at the electrode-electrolyte interface of a water-splitting, electrochemical cell using particle image velocimetry (PIV) and planar laser-induced fluorescence (PLIF). In a water-splitting device, mass transfer mechanisms usually involve simultaneous convection, diffusion, and migration. Mass transfer rate, at the electrode/electrolyte interface, depends on various factors, including electrode orientation, current density, type of redox agents and the products. The parameters considered here are cell voltage, the orientation of electrode, and the effect of concentration gradient induced by the reactants depletion and product formation at the interface on the mass transfer rate. The present study captures the instantaneous velocity and concentration fields using PIV and PLIF techniques. Conducting the experiments over various current densities and electrode-orientations, present study observes that the reactant depletion and product formation at the anode interface induces buoyancy which in turn causes natural convection even at low current densities. By utilizing the effect of orientation and the natural convection induced by the reactants and products, on the mass transfer rate, the limiting current density can be enhanced, and the supersaturation of products can be prevented at the interface.

Topical application of antimicrobials at the site of infection offer greater advantages as compared to systemic therapy. The present study reports for the first time, the in vivo wound healing potential of an herbal antimicrobial gel containing pure bioactive leaf extract of Cassia alata L. The methanolic leaf extract exhibited significant antibacterial and antifungal activity against the tested bacteria (Staphylococcus aureus MTCC 9542) and fungi (Candida albicans MTCC 4842) due to the presence of alcohol and ketone containing bioactive moieties. A 1% (w/w) bioactive leaf extract based-hydrogel was formulated and evaluated for its wound healing potential in rat model with surgical site infection in the dorsal area. This herbal gel significantly enhanced the wound healing as assessed by the contraction of wound length and bio burden characteristics compared to the marketed antimicrobial formulations. The formulated herbal gel could find use as very promising and innovative topical alternative for the treatment of skin infections caused by bacteria as well as fungal strains without hazard to human health based on the fact of its traditional use by the Assamese people with no toxic effects. Keywords: Cassia alata L.; methanolic leaf extracts; antimicrobial gel; antibacterial; antifungal; wound healing

The objective of the present investigation was to optimize and develop Tenofovir Disoproxil Fumarate (TDF) loaded Nanostrucrured Lipid Carriers (NLCs) with Compritol 888 ATO as solid lipid and oleic acid as liquid lipid by modified emulsion solvent diffusion method using Central Composite design (CCD). Three independent variables viz., Lipid to Drug ratio (A), Aqueous phase pH (B) and Sonication time (min) (C) were taken to investigate their effect on dependent variables viz., particle size (nm) (R1), PDI (R2) and % Entrapment Efficiency (%EE) (R3). Optimized formula of NLC was selected from the design space which was further optimized by changing the surfactants quantity. NLCs were evaluated for physicochemical, morphological, solid state characterization, and in-vitro dissolution in PBS pH 6.4, PBS 7.4 and ACSF. The average particle size was found to be 94.7 ± 15.70 nm with PDI of 0.380 ± 0.024 and 134.3 ± 9.71 nm with PDI of 0.358 ± 0.038 respectively for T4 and T5 NLC formulation. The zeta potential value of -17. ± 3.87 mV and -17.17 ± 1.05 mV and %EE of 35.5 ± 1.04 % and 34.2 ± 2.78 %. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. Keywords: Central composite design, Intranasal, Neuro-AIDS, CNS targeting.

Objective: Site-specific drug delivery into the colonic region is extremely fascinating for local treatment of various colonic diseases like ulcerative colitis, colon cancer but it should be capable of saving the drug from hydrolysis and degradation. The present study reports the application of jackfruit seed starch and its thiol derivative as a drug delivery carrier for the colon. Methods: The starch was extracted from the jackfruit seeds by water extraction method and modified by the esterification reaction with thioglycolic acid. The thiolated starch was characterized for morphology, functional and flow properties. The safety profile of the thiolated starch was confirmed by acute toxicity study in a mice model as per OECD guidelines 423. The microspheres based on thiolated starch were prepared by ionic gelation method incorporating Ibuprofen as a model drug. The prepared microspheres were characterized for particle size, drug entrapment efficiency, drug loading, compatibility study, surface morphology, in vitro drug release and release kinetics. Results: The result attributed that starch was successfully modified by the thiolation with a degree of substitution of 3.30. The size of prepared microspheres ranges from 825.5±4.58 to 857±6.24 µm, the entrapment efficiencies ranges from 69.23±1.19 to 76.15±0.83 % and the drug loading capacity ranges from 17.75±0.30 to 46.05±0.49 %. The FT-IR, DSC and XRD studies confirmed that there is no interaction within drug and excipients. The thiolated starch microspheres show the maximum release of drug at pH 7.4 in the presence of rat caecal content as compared to pH 1.2 and pH 6.8 for up to 24 h and are following first order release kinetics. Conclusion: These results suggest the application of thiolated jackfruit seed starch could be promising as a long-term drug delivery carrier for the colon.

Many advanced schlieren systems have been reported in the literatures and a great number of it are associated in gas flow study, commonly air. Present research proposes an efficient use of Z-type schlieren technique for simultaneous measurement of ray-averaged velocity as well as temperature fields beside qualitative flow visualization. Experiments are conducted to study natural convective flow in de-ionized water in a differentially heated cubical enclosure. The same set of transient schlieren images has been used for simultaneous measurement of velocity and temperature field. The velocity field is also determined by using laser based particle image velocimetry (PIV) to compare with schlieren based technique. The developed schlieren system has been used to obtain ray-averaged quantities, such as, thermal and hydrodynamic boundary layer thicknesses, temperature gradient and temperature fields, distribution of local Nusselt number along the thermally active walls, average Nusselt number and velocity field. In this work, the above quantities have been simultaneously determined for the first time using halogen projector lamp based Z-type calibration schlieren system. The results inspire the use of calibration schlieren system for the study of natural convective flow in water-filled cubical enclosures. The above results also provide experimental data as new benchmark for researchers to compare results for high Rayleigh number free convective flow with water as the working medium.

Shape memory polymer (SMP) foam is often proposed as the future alternative of coils in aneurysm treatment devices. Present work numerically investigates the unsteady, three-dimensional simulation of blood flow in a cerebral aneurysm filled with SMP foam. Simulations are conducted on patient-specific geometries with realistic blood velocity waveform imposed at the inlet while SMP foam is treated as a porous medium. The present study introduces a “loading risk map” that helps to visualize the hemodynamic effect of foam insertion on the aneurysm sac and neck. The loading risk maps suggest that while the SMP foam subdues the flow and wall shear pulsations in the aneurysm sac, the pressure distribution is minimally affected. The maps suggest that while the downstream lip is the most risk-prone site for both geometries, downstream vascular anatomy significantly influences foam efficiency in reducing pressure and wall shear stress loading.

Fluid, heat and species transport and oxygen reduction in the cathode of a PEM fuel cell are simulated using multi relaxation lattice Boltzmann method. Heat generation due to oxygen reduction and its effects on transport and reaction are considered. Simulations for various cell operating voltages, temperatures and flow rates with various values of porous media properties, namely, permeability, porosity, and effective porous media diffusion coefficient, are performed to study transport and operating characteristics in the electrode. It is seen that maximum output power density achievable is limited by the mass transport rate. A small increase in current density is obtained by increasing the operating temperature. However, this results in an increase in the rate of heat generation. Permeability and porosity of the gas diffusion layer do not show a significant impact on the performance in the range of values presently simulated. Higher permeability, in turn, resulted in enhancement of thermal gradients in the porous layer. A significant increase in the maximum current density obtainable is observed with increase in flow rates. The higher convection associated with high flow rate facilitates better transport of species and heat at the catalyst layer resulting in larger current density with a lesser chance of hotspot formation. Increased species diffusion coefficient also resulted in increasing the power output substantially. In addition, the fuel utilization is also improved at high diffusion rates in the porous media. The study analyses and shows the impact of various operating and material parameters affecting the performance of a PEM fuel cell with special attention on enhancing the maximum power density attainable.

This article aims to numerically investigate the combustion phenomenon of coaxial gaseous CH4 LOx at supercritical pressures. The choice of turbulence model, real gas model, and chemical kinetics model are the critical parameters in numerical simulations of cryogenic combustion at high pressure. At this supercritical operating pressure, the ideal gas law does not remain valid for such cases. Therefore, we have systematically carried out a comparative study to analyze the importance of real gas models, turbulence parameters, and chemical kinetics at such conditions. The comparison of real gas models with the NIST database reveals better conformity of SRK (Soave Redlich Kwong Equation of State (EoS)) model predictions with the database. Further, the computed results indicate that the Standard k-e turbulence model with modified constant captures the better flame shape and temperature peak position compared to other RANS based turbulence models while invoking the non-premixed steady b-PDF flamelet model for simulating the combustion process. Furthermore, a comparative study comparing two different chemical kinetics models indicates that the reduced Jones Lindstedt mechanism can accurately predict the flame characteristics with the least computational cost. Finally, we have studied the effect of chamber pressure and LOx inlet temperature on the flame characteristics. The flame characteristics exhibit a strong sensitivity towards the chamber pressure due to the weakening of the pseudo-boiling effect with an increase in pressure. As a consequence of lower turbulent rates of energy and mass transfer through the transcritical mixing layer, the flame spreading becomes narrower at elevated pressure and temperature, thereby yielding an increased flame length at transcritical conditions.

The progress of the nanotechnology in the precinct of biomedicine has been outlandish with the successful developments of nanomedicines as well as nanomaterials intended for diagnosis purpose. However, a more sophisticated system blurring the line between diagnosis and therapy has come into the picture. And, this particular intervention is termed as “Theranostics,” which merge these two modalities in order to furnish a synergistic action where the imaging modality not only screens the pre and post but also throughout the entire treatment regimen. When nanomaterials are exploited with intend to actualize theranostic resolve, it is termed as “Nanotheranostics.” This chapter throws light on the aspects, factors to consider, and the components involved for engineering theranostic nanoparticles. An attempt has also been made to canvas the toxicological considerations of the theranostic nanoparticles. Finally, the challenges posing as an obstruction in the translation of theranostic nanoparticles to clinic has been recounted.

Hemodynamics of a stenosed cerebral artery is discussed in this work. An unsteady, unstructured 2D solver is developed and used for the simulations. Flow is solved for physiologically realistic inlet flow waveform. Investigative focus is on the vortex dynamics and effect of Fourier modes of the waveform. Level and features of vortex structures are studied and compared. Most important Fourier mode for reproducing the flow structures is discussed, and differences are analysed.

Cancer theranostic is the integration of imaging and chemotherapy for the treatment of various types of cancer. Gold nanostars are unique nanoparticles with multiple sharp tips and edges which provide enhanced sensitivity toward various imaging and contrast agents for cancer theranostics. They are biocompatible nanoplatform for photothermal and photodynamic therapy. They can also be functionalized with targeting moieties and chemotherapeutic agents can be attached to provide multifunctionality to these unique nanoparticles. This chapter provides the recent advances in various methods of synthesis and their application in biosensing, imaging, and tumor ablation. The safety or toxicity issue with gold nanoparticles as a whole is also highlighted.

This review summarizes the aspects of noninvasive imaging techniques for diagnosis and treatment of disease promoting prognosis of personalized medicine. Nanoparticles-based imaging techniques, also known as “Nanotheranostics,” are widely used for this purpose. Basically, noninvasive medical imaging techniques such as magnetic resonance imaging, X-ray computed tomography, positron emission tomography, single photon emission computed tomography, and optical imaging assist diagnosis, localization, biodistribution, and pharmacokinetics study of nanoparticles using molecular imaging probe such as radionuclides and flourophores. Use of nanotheranostics facilitates target-specific delivery, high-contrast and high-resolution imaging, low dose requirement, multimodal imaging, easy surface modification, and targeted organ imaging. Thus, multimodal imaging-based multifunctional nanotheranostics enables real-time imaging, higher biodistribution in targeted organs or tissues, and pharmacokinetic study of drug especially for cancer treatment.

The present study investigates the influence of surfactant crowding on hydrate growth and detachment of hydrate crystal from the interface in a droplet-based configuration. Experiments were conducted under a constant subcooling of 5 °C using a cyclopentane droplet of volume 5 μL immersed in the water pool. Sorbitan Monooleate (Span 80) was used as a surfactant at various concentrations below and above critical micelle concentration (CMC). Hydrate forming droplet images were captured in backlight illumination. The centroid of the droplet was also tracked to explain the morphological changes during hydrate formation. Surfactant crowding occurs due to rearrangement of surfactants at the guest-water interface during clathrate hydrate growth. The presence of surfactant encouraged radial hydrate growth and formation of hydrate columns. The effect of radial growth manifested in form of dramatic rise in the vertical position of the centroid, that is, 125.15% higher than no surfactant case for 0.00143% v/v surfactant concentration. The hydrate crystals detach after the initial growth period for surfactant concentrations closer to 10% CMC. The forces affecting the crystal detachment process are illustrated, and an approximate mathematical model was proposed to find the height of the crystal for initiation of detachment of the crystal. The analysis revealed that crystals with a narrow base tend to gain more height vertically before detachment, complementing experimental observations. Overall, the present study illustrates the significant role of surfactant crowding in modifying the hydrate growth process and morphology. The detachment of the hydrate crystals from the interface can serve as an alternative mechanism for rapid hydrate growth during the presence of surfactant.