Skin temperature oscillation model for assessing vasomotion of microcirculation

It has been proved that there exists a certain correlation between fingertip temperature oscillations and blood flow oscillations. In this work, a porous media model of human hand is presented to investigate how the blood flow oscillation in the endothelial frequency band influences fingertip skin temperature oscillations. The porosity which represents the density of micro vessels is assumed to vary periodically and is a function of the skin temperature. Finite element analysis of skin temperature for a contra lateral hand under a cooling test was conducted. Subsequently, wavelet analysis was carried out to extract the temperature oscillations of the data through the numerical analysis and experimental measurements. Furthermore, the oscillations extracted from both numerical analyses and experiments were statistically analyzed to compare the amplitude. The simulation and experimental results show that for the subjects in cardiovascular health, the skin temperature fluctuations in endothelial frequency decrease during the cooling test and increase gradually after cooling, implying that the assumed porosity variation can represent the vasomotion in the endothelial frequency band.     

磁性靶向药物递送中铁磁流体的动力学建模

Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application.     

Magnetic nanoparticle drug targeting to patient-specific atherosclerosis: effects of magnetic field intensity and configuration

Nanoparticle-mediated drug delivery is recognized as a promising option for targeted treatment of atherosclerosis. In this paper, the Eulerian-Lagrangian technique is adopted to simulate the delivery of drug-loaded nanoparticles to patient-specific atherosclerotic plaque with the aid of an external magnetic field. Plaques and vascular walls are introduced as porous media formulated by the Darcy-Forchheimer model in this targeted transport process. The results demonstrate that the delivery efficiency of particles to atherosclerosis depends on the external magnetic field, such as configuration and intensity, in which the configuration angle of the current wire is a key factor and the double current wires have advantages over the single current wire. Meanwhile, the delivery efficiency gradually decreases as the distance between the plaque cap and the current wire increases. Further, although augmenting the current or magnetic susceptibility can generally improve the delivery efficiency of nanoparticles, this increase is not apparent when small-sized nanoparticles are employed as drug transport particles. The results obtained can potentially serve as the guideline to optimize regimens for the targeted therapy of atherosclerosis.     

Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.     

Virtual experimentation through 3D full-loop simulation of a circulating fluidized bed

Eulerian granular multiphase model with a drag coefficient correction based on the energy-minimization multi-scale （EMMS） model was used to simulate a semi-industry scale circulating fluidized bed （CFB）. Three-dimensional （3D）, time-dependent simulation of a full-loop CFB revealed that the axial profiles of cross-sectionally averaged solid volume fraction, and the radial profiles of solid axial velocity and solid volume fraction were in reasonable agreement with experimental data. Based on this agreement, database derived from experiments not yet accomplished was replenished with such simulations, and fluid regime diagrams and pressure balance around the CFB loop were derived accordingly. This work presents an integrated viewpoint on CFB and unfolds a fresh paradigm for CFB modeling, which can be expected to help resolve certain issues long in dispute but bard for experiments.     

Modeling of particle transport and combustion phenomena in a large-scale circulating fluidized bed boiler using a hybrid Euler-Lagrange approach

The constantly developing fiuidized combustion technology has become competitive with a conventional pulverized coal （PC） combustion. Circulating fluidized bed （CFB） boilers can be a good alternative to PC boilers due to their robustness and lower sensitivity to the fuel quality. However, appropriate engineering tools that can be used to model and optimize the construction and operating parameters of a CFB boiler still require development. This paper presents the application of a relatively novel hybrid Euler-Lagrange approach to model the dense gas-solid flow combined with a combustion process in a large-scale indus- trial CFB boiler. In this work, this complex flow has been resolved by applying the ANSYS FLUENT 14.0 commercial computational fluid dynamics （CFD） code. To accurately resolve the multiphase flow, the original CFD code has been extended by additional user-defined functions. These functions were used to control the boiler mass load, particle recirculation process （simplified boiler geometry）, and interphase hydrodynamic properties. This work was split into two parts. In the first part, which is referred to as pseudo combustion, the combustion process was not directly simulated. Instead, the effect of the chemi- cal reactions was simulated by modifying the density of the continuous phase so that it corresponded to the mean temperature and composition of the flue gases, In this stage, the particle transport was simu- lated using the standard Euler-Euler and novel hybrid Euler-Lagrange approaches, The obtained results were compared against measured data, and both models were compared to each other. In the second part, the numerical model was enhanced by including the chemistry and physics of combustion. To the best of the authors＇ knowledge, the use of the hybrid Euler-Lagrange approach to model combustion is a new engineering application of this model, In this work, the combustion process was modeled for air-fuel combustion. The simulation results were compared with experimental data.     

FLUIDIZATION OF FINE POWDERS IN FLUIDIZED BEDS WITH AN UPWARD OR A DOWNWARD AIR JET

The hydrodynamic behavior of fine powders in jet-fluidized beds was studied numerically and experimentally. The starting point of numerical simulation was the generalized Navier-Stokes (N-S) equations for the gas and solids phases. The K-εturbulence model was used for high-speed gas jets in fluidized beds. Computation shows that a suitable turbulence model is necessary to obtain agreement between the simulation and literature experimental data for a high-speed gas jet. The model was applied to simulating the fluidization of fine powders in fluidized beds with an upward or a downward air jet. An empirical cohesion model was obtained by correlating the cohesive force between fine particles using a cohetester. The cohesion model was embedded into the two-fluid model to simulate the fluidization of fine powders in two-dimensional (2-D) beds. To study the fluidization behavior of fine and cohesive powders with a downward jet,experiments were performed in a 2-D bed. Agreement between the computed time-averaged porosity and measured data was obtained. With an upward jet in the bed center, the measured and computed porosities show a dilute centralcore, especially at very high jet velocities. Based on our experiments and computations, a downward jet located inside the bed is recommended to achieve better mixing and contacting of gas and solids.     

A CREEP DAMAGE EQUATION FOR ROCKS

In this paper,based on many experimental results,a creep damageequation for rocks with a creep modulus that can describe the history of damage hasbeen deduced.According to the equation,a creep damage model for rock materials isconstructed,and it is shown that the extent of their damage,or damage degree,duringcreep can be determined by means of simple experiments.     

A novel triple periodic minimal surface-like plate lattice and its data-driven optimization method for superior mechanical properties

Lattice structures can be designed to achieve unique mechanical properties and have attracted increasing attention for applications in high-end industrial equipment,along with the advances in additive manufacturing(AM) technologies. In this work, a novel design of plate lattice structures described by a parametric model is proposed to enrich the design space of plate lattice structures with high connectivity suitable for AM processes. The parametric model takes the basic unit of the triple perio...     

Modeling ocean wave propagation under sea ice covers

Operational ocean wave models need to work globally, yet current ocean wave models can only treat ice covered regions crudely. The purpose of this paper is to provide a brief overview of ice effects on wave propagation and different research methodology used in studying these effects. Based on its proximity to land or sea, sea ice can be classified as: landfast ice zone, shear zone, and the marginal ice zone. All ice covers attenuate wave energy. Only long swells can penetrate deep into an ice cover. Being closest to open water, wave propagation in the marginal ice zone is the most complex to model. The physical appearance of sea ice in the marginal ice zone varies. Grease ice, pancake ice,brash ice, floe aggregates, and continuous ice sheet may be found in this zone at different times and locations. These types of ice are formed under different thermal-mechanical forcing. There are three classic models that describe wave propagation through an idealized ice cover: mass loading,thin elastic plate, and viscous layer models. From physical arguments we may conjecture that mass loading model is suitable for disjoint aggregates of ice floes much smaller than the wavelength, thin elastic plate model is suitable for a continuous ice sheet, and the viscous layer model is suitable for grease ice. For different sea ice types we may need different wave ice interaction models. A recently proposed viscoelastic model is able to synthesize all three classic models into one. Under suitable limiting conditions it converges to the three previous models. The complete theoretical framework for evaluating wave propagation through various ice covers need to be implemented in the operational ocean wave models. In this review, we introduce the sea ice types, previous wave ice interaction models, wave attenuation mechanisms,the methods to calculate wave reflection and transmission between different ice covers, and the effect of ice floe breaking on shaping the sea ice morphology. Laboratory experiments,field measurements and numerical simulations supporting the fundamental research in wave-ice interaction models are discussed. We conclude with some outlook of future research needs in this field.     

Hydrodynamic modelling and CFD simulation of ferrofluids flow in magnetic targeting drug delivery

Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a tissue target in the human body under the applied magnetic field. This method increases the drug concentration in the target and reduces the adverse side-effects. In this article, a mathematical model is presented to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. Numerical simulations are performed to obtain better insight into the theoretical analysis with computational fluid dynamics. A 3D flow field of magnetic particles in an idealised blood vessel model containing an aneurysm is analysed to further understand clinical application of magnetic targeting drug delivery. Simulation samples demonstrate the important parameters leading to adequate drug delivery to the target site depending on the applied magnetic field in coincidence with reported results from animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favour of the clinical application.     

Size-dependent cellular uptake and sustained drug release of PLGA particles

Poly (lactic-co-glycolic) acid (PLGA) particles have become a commonly used drug delivery strategy in the pharmaceutical industry. In this work, we aim to investigate the size-dependent cellular internalization of PLGA particles and its effects on sustained drug release. We prepared three different-sized particles using PLGA (200, 500 and 2000 nm) ranging from submicrometer to micrometer. Dexamethasone (DEX) with excellent anti-inflammatory properties was used as a model drug to prepare DEX-loaded PLGA particles (DPs). We comprehensively investigated the encapsulation efficiency, cellular uptake and in vitro drug release profile. Pharmacodynamic assessment revealed that, in the lipopolysaccharide (LPS)-induced RAW 264.7 cells model, 500 nm DPs showed sustained anti-inflammatory efficacy. This work provides important information for designing PLGA-based drug delivery systems for biomedical applications.     

A critical review of ferritin as a drug nanocarrier: Structure,properties, comparative advantages and challenges

Ferritin stores and releases iron ions in mammals. It is globally important as a drug nanocarrier. This is because of its unique hollow-spherical structure, desirable stability and biological properties. Novel drug-loading approaches plus various functionalization approaches have been developed to improve ferritin in response to differing demands in disease treatments. Here, we critically review ferritin drug delivery and evaluate its diverse drug-loading and functionalization approaches, we: (1) Introduce basic structural and property information related to ferritin as a drug nanocarrier; (2) Contrast in detail the different means to load drugs and the selection of drug loading means; (3) Discuss multiple ferritin functionalization approaches, together with related advantages and potential risks; and, (4) Compare ferritin with alternative, commonly-used drug nanocarriers. We conclude that despite that no drugs based on ferritin are commercially available, the market potential for it is significant, and evaluate future research directions. Findings from this work will be of immediate benefit and interest to a wide range of researchers and manufacturers for drug delivery using ferritin.     

Engineering of drug nanoparticles by HGCP for pharmaceutical applications

This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nenoparticles, which was carded out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxirne Axetil (CFA) particles, 200-400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), end 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation end drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing end the ease of scaling-up.     

Gas and Particle Dynamics of a Contoured Shock Tube for Pre-clinical Microparticle Drug Delivery

We investigate the gas-particle dynamics of a device designed for biological pre-clinical experiments. The device uses transonic/supersonic gas flow to accelerate microparticles such that they penetrate the outer skin layers. By using a shock tube coupled to a correctly expanded nozzle, a quasi-one-dimensional, quasi-steady flow (QSF) is produced to uniformly accelerate the microparticles. The system utilises a microparticle “cassette” (a diaphragm sealed container) that incorporates a jet mixing mechanism to stir the particles prior to diaphragm rupture. Pressure measurements reveal that a QSF exit period – suitable for uniformly accelerating microparticles – exists between 155 and 220 mus after diaphragm rupture. Immediately preceding the QSF period, a starting process secondary shock was shown to form with its (x,t) trajectory comparing well to theoretical estimates. To characterise the microparticle, flow particle image velocimetry experiments were conducted at the nozzle exit, using particle payloads with varying diameter (2.7–48 μm), density (600–16,800 kg/m³) and mass (0.25–10 mg). The resultant microparticle velocities were temporally uniform. The experiments also show that the starting process does not significantly influence the microparticle nozzle exit velocities. The velocity distribution across the nozzle exit was also uniform for the majority of microparticle types tested. For payload masses typically used in pre-clinical drug and vaccine applications (≤ 1 mg), it was demonstrated that payload scaling does not affect the microparticle exit velocities. These characteristics show that the microparticle exit conditions are well controlled and are in agreement with ideal theory. These features combined with an attention to the practical requirements of a pre-clinical system make the device suitable for investigating microparticle penetration into the skin for drug delivery.     

Plasma protein corona forming upon fullerene nanocomplex: Impact on both counterparts

Protein corona refers to the structure composed of biomolecules adsorbed on the surface of nanomaterials. The study on the effect of the interaction between protein and nanoparticles can provide an important guide for the application of nanodrug delivery. To provide a reference for the research on fullerene (C60) nanocomplex drug delivery systems, this work studied the interaction between C60 nanocomplex and a variety of plasma proteins. Research showed that the protein binding with C60 nanocomplex did not change the charge properties of protein. The proteins induced the aggregation of C60 nanocomplex. The circular dichroism spectra showed that the secondary structure of the proteins changed after binding to C60 nanocomplex. The ultraviolet–visible spectra showed that the effect of C60 nanocomplex on proteins was concentration-dependent. The fluorescence spectra showed that C60 nanocomplex could intrinsic fluorescence alteration of proteins. The adsorption capacity of C60 nanocomplex to proteins was changed at 0 h and 4 h. The interaction between nanocomplex and proteins might affect the morphological characteristics of nanocomplex and the conformation of proteins. This work could provide a reference for the research and development of C60 nanocomplex and other carbon-based nanocomplex as nanoparticulate drug delivery systems.     

A new biolistic intradermal injector

We present a novel intradermal needle-free drug delivery device which exploits the unsteady high-speed flow produced by a miniature shock tube to entrain drug or vaccine particles onto a skin target. A first clinical study of pain and physiological response of human subjects study is presented, comparing the new injector to intramuscular needle injection. This clinical study, performed according to established pain assessment protocols, demonstrated that every single subject felt noticeably less pain with the needle-free injector than with the needle injection. Regarding local tolerance and skin reaction, bleeding was observed on all volunteers after needle injection, but on none of the subjects following powder injection. An assessment of the pharmacodynamics, via blood pressure, of pure captopril powder using the new device on spontaneously hypertensive rats was also performed. It was found that every animal tested with the needle-free injector exhibited the expected pharmacodynamic response following captopril injection. Finally, the new injector was used to study the delivery of an inactivated influenza vaccine in mice. The needle-free device induced serum antibody response to the influenza vaccine that was comparable to that of subcutaneous needle injection, but without requiring the use of an adjuvant. Although no effort was made to optimize the formulation or the injection parameters in the present study, the novel injector demonstrates great promise for the rapid, safe and painless intradermal delivery of systemic drugs and vaccines.     

The role of porous media in biomedical engineering as related to magnetic resonance imaging and drug delivery

Pertinent works associated with magnetic resonance imaging (MRI) and drug delivery are reviewed in this work to demonstrate the role of transport theory in porous media in advancing the progress in biomedical applications. Diffusion process is considered significant in many therapies such as delivering drugs to the brain. Progress in development of the diffusion equation using local volume-averaging technique and evaluation of the applications associated with the diffusion equation are analyzed. Tortuosity and porosity have a significant effect on the diffusion transport. Different relevant models of tortuosity are presented and mathematical modeling of drug release from biodegradable delivery systems are analyzed in this investigation. New models for the kinetics of drug release from porous biodegradable polymeric microspheres under bulk erosion and surface erosion of the polymer matrix are presented in this study. Diffusion of the dissolved drug, dissolution of the drug from the solid phase, and erosion of the polymer matrix are found to play a central role in controlling the overall drug release process. This study paves the road for the researchers in the area of MRI and drug delivery to develop comprehensive models based on porous media theory utilizing fewer assumptions as compared to other approaches.