Analysis of improved oral drug delivery with different helical stream inhalation modes.

A challenging aspect of pulmonary drug delivery devices, e.g., metered dose inhalers (MDIs), is to deliver therapeutic drugs to prescribed target locations at the required dosage level.

Improving Pulmonary Nanotherapeutics Using Helical Aerosol Streams: An In Silico Study.

The increasing prevalence of pulmonary ailments including asthma, chronic obstructive pulmonary disorder, lung tuberculosis, and lung cancer, coupled with the success of pulmonary therapy, has led to a plethora of scientific research focusing on improving the efficacy of pulmonary drug delivery systems. Recent advances in nanoscience and nano-engineering help achieve this by developing stable, potent, inhalable nanosize drug formulations that potentially increase dosages at target sites with significant therapeutic effects. In this study, we numerically analyze a novel methodology of incorporating helical air-nanoparticle streams for pulmonary nanotherapeutics, using a customized version of the open-source computational fluid dynamics (CFD) toolbox openfoam.

Comparison of micron- and nano-particle transport in the human nasal cavity with a focus on the olfactory region.

Intranasal administration of drugs serves as a promising, noninvasive option for the treatment of various disorders of the central nervous system and upper respiratory tract. Predictive, ie, realistic and accurate, particle tracking in the human nasal cavities is an essential step to achieve these goals. The major factors affecting aerosol transport and deposition are the inhalation flowrate, the particle characteristics, and the nasal airway geometry.

Modeling Airflow and Particle Deposition in a Human Acinar Region.

The alveolar region, encompassing millions of alveoli, is the most vital part of the lung. However, airflow behavior and particle deposition in that region are not fully understood because of the complex geometrical structure and intricate wall movement. Although recent investigations using 3D computer simulations have provided some valuable information, a realistic analysis of the air-particle dynamics in the acinar region is still lacking.

Mice-to-men comparison of inhaled drug-aerosol deposition and clearance.

Part of the effective prediction of the pharmacokinetics of drugs (or toxic particles) requires extrapolation of experimental data sets from animal studies to humans. As the respiratory tracts of rodents and humans are anatomically very different, there is a need to study airflow and drug-aerosol deposition patterns in lung airways of these laboratory animals and compare them to those of human lungs. As a first step, interspecies computational comparison modeling of inhaled nano-to-micron size drugs (50 nm < d<15μm) was performed using mouse and human upper airway models under realistic breathing conditions.

Direct nanodrug delivery for tumor targeting subject to shear-augmented diffusion in blood flow.

The advent of multifunctional nanoparticle has enabled numerous innovative strategies in diagnostics, imaging, and cancer therapy. Despite the intense research efforts in developing new nanoparticles and surface bonding ligands, one major obstacle in achieving highly effective treatment, including minimizing detrimental side effects, is the inability to deliver drug-carrying nanoparticles from the injection point directly to the tumor site. The present study seeks to employ a direct nanodrug delivery methodology to feed multifunctional nanoparticles directly to tumor vasculatures, sparing healthy tissue.

Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome.

Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies.

Hemodynamic Parameters and Early Intimal Thickening in Branching Blood Vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation.

Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing.

Solid Tumor Embolotherapy in Hepatic Arteries with an Anti-reflux Catheter System.

Unresectable hepatoma accounts for the majority of malignant liver tumor cases for which embolization therapy is considered a viable treatment option. However, the potential risk of aberrant particle deposition in non-target regions could cause severe side-effects, alongside diminished efficacy. A computational model has been developed to analyze the particle-hemodynamics before and after deployment of an FDA-approved anti-reflux catheter.

A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model.

Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume.

Drug-targeting methodologies with applications: A review.

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity.

Lung deposition analyses of inhaled toxic aerosols in conventional and less harmful cigarette smoke: a review.

Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions.

Impact of fluid-structure interaction on direct tumor-targeting in a representative hepatic artery system.

Direct targeting of solid tumors with chemotherapeutic drugs and/or radioactive microspheres can be a treatment option which minimizes side-effects and reduces cost. Briefly, computational analysis generates particle release maps (PRMs) which visually link upstream particle injection regions in the main artery with associated exit branches, some connected to tumors. The overall goal is to compute patient-specific PRMs realistically, accurately, and cost-effectively, which determines the suitable radial placement of a micro-catheter for optimal particle injection.

Nanoparticle mass transfer from lung airways to systemic regions--Part II: Multi-compartmental modeling.

This is the second article of a two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer, 2013, "Nanoparticle Mass Transfer From Lung Airways to Systemic Regions--Part I: Whole-Lung Aerosol Dynamics," ASME J. Biomech. Eng.

Nanoparticle mass transfer from lung airways to systemic regions--Part I: Whole-lung aerosol dynamics.

This is a two-part paper describing inhaled nanoparticle (NP) transport and deposition in a model of a human respiratory tract (Part I) as well as NP-mass transfer across barriers into systemic regions (Part II). Specifically, combining high-resolution computer simulation results of inhaled NP deposition in the human airways (Part I) with a multicompartmental model for NP-mass transfer (Part II) allows for the prediction of temporal NP accumulation in the blood and lymphatic systems as well as in organs. An understanding of nanoparticle transport and deposition in human respiratory airways is of great importance, as exposure to nanomaterial has been found to cause serious lung diseases, while the use of nanodrugs may have superior therapeutic effects.

Computational analysis of non-spherical particle transport and deposition in shear flow with application to lung aerosol dynamics--a review.

All naturally occurring and most man-made solid particles are nonspherical. Examples include air-pollutants in the nano- to micro-meter range as well as blood constituents, drug particles, and industrial fluid-particle streams. Focusing on the modeling and simulation of inhaled aerosols, theories for both spherical and nonspherical particles are reviewed to analyze the contrasting transport and deposition phenomena of spheres and equivalent spheres versus ellipsoids and fibers.

Experimental microsphere targeting in a representative hepatic artery system.

Recent work employing the computational fluid-particle modeling of the hepatic arteries has identified a correlation between particle release position and downstream branch distribution for direct tumor-targeting in radioembolization procedures. An experimental model has been constructed to evaluate the underlying simulation theory and determine its feasibility for future clinical use. A scaled model of a generalized hepatic system with a single inlet and five outlet branches was fabricated to replicate the fluid dynamics in the hepatic arteries of diseased livers.

Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review.

Correction to Kleinstreuer C, Feng Y: Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review. Nanoscale Research Letters 2011, 6:229.

Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review.

Nanofluids, i.e., well-dispersed (metallic) nanoparticles at low- volume fractions in liquids, may enhance the mixture's thermal conductivity, knf, over the base-fluid values.

Deposition of naphthalene and tetradecane vapors in models of the human respiratory system.

Jet-propulsion fuel (particularly JP-8) is currently being used worldwide, exposing especially Air Force personnel and people living near airfields to JP-8 vapors and aerosols during aircraft fueling, maintenance operations, and/or cold starts. JP-8 is a complex mixture containing >200, mostly toxic, aliphatic and aromatic hydrocarbon compounds of which tetradecane and naphthalene were chosen as two representative chemical markers for computer simulations. Thus, transport and deposition of naphthalene and tetradecane vapors have been simulated in models of the human respiratory system.

Computer modeling of controlled microsphere release and targeting in a representative hepatic artery system.

Combating liver tumors via yttrium-90 ((90)Y) radioembolization is a viable treatment option of nonresectable liver tumors. Employing clinical (90)Y microparticles (i.e.

Computer modeling of yttrium-90-microsphere transport in the hepatic arterial tree to improve clinical outcomes.

Purpose: Radioembolization (RE) via yttrium-90 ((90)Y) microspheres is an effective and safe treatment for unresectable liver malignancies. However, no data are available regarding the impact of local blood flow dynamics on (90)Y-microsphere transport and distribution in the human hepatic arterial system.

Methods And Materials: A three-dimensional (3-D) computer model was developed to analyze and simulate blood-microsphere flow dynamics in the hepatic arterial system with tumor.

Airflow and nanoparticle deposition in a 16-generation tracheobronchial airway model.

In order to achieve both manageable simulation and local accuracy of airflow and nanoparticle deposition in a representative human tracheobronchial (TB) region, the complex airway network was decomposed into adjustable triple-bifurcation units, spreading axially and laterally. Given Q(in) = 15 and 30 L/min and a realistic inlet velocity profile, the experimentally validated computer simulation model provided some interesting 3-D airflow patterns, i.e.