In silico investigation of the effect of particle diameter on deposition uniformity in pulmonary drug delivery

Systemic drug delivery via the pulmonary route has a critical limitation because dose uniformity is strongly dependent upon patient inhalation technique. The most frequent and critical errors in inhalation technique are overly forceful inspiration and insufficient breath-holding. In this study, response surface methodology was used with an in silico whole lung particle deposition model for bolus administration to investigate whether varying the inhaled drug particle size could reduce the dependence of deposition upon flow rate and/or breath-holding duration. The range of particle aerodynamic diameters studied was 0.1–10 µm for flow rates between 500–2000 mL/s and breath-holding duration between 0–15 seconds. Comparison with published experimental data showed that this modeling approach can accurately predict the lung deposition. The simulation results indicated that the deposition of particles with aerodynamic diameter in the range of 0.1–1.5 µm should be minimally affected by flow rate over the 500–2000 mL/s range. There was found to be no particle size whose deposition was completely independent of breath-holding duration. The smallest particles, whose deposition is diffusion-driven, were found to be the least sensitive to breath-holding time, but this size is of limited practical use. On the other hand, the simulations indicated that particles with a 1.5 µm diameter would provide acceptable consistency in dose reaching the acini region when the breath-holding duration was greater than 10 seconds. It is hoped that this finding could provide a means of improving dose uniformity for systemic delivery via the pulmonary route by facilitating simplified patient instructions

Dissolution of coated microbubbles: The effect of nanoparticles and surfactant concentration

The ability of solid particles to stabilise emulsions is a well known phenomenon which has recently been demonstrated for the stabilisation of gas bubbles. In this paper, a new theoretical model is developed which describes how an adsorbed layer of solid nanoparticles modifies the interfacial tension and diffusivity of a gas bubble in a liquid and hence its stability. In agreement with experimental observations on microbubbles coated with 15 nm diameter spherical gold particles, the results of simulations with the model indicate that the particles substantially decrease the rate at which bubble dissolution occurs and enables them to maintain a stable radius once a critical particle concentration has been reached

Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy.

Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art

Preparation of a micro-porous alginate gel using a microfluidic bubbling device

Demand for low-energy food products has greatly increased in recent years due to the growing concerns over obesity related health problems. The aim of the work described in this short communication was to use a microfluidic T-junction device to prepare microporous calcium alginate gels by incorporating monodisperse air bubbles (177 μm in diameter) which would both increase the volume to energy content ratio of the product and improve sample homogeneity. Homogeneous, 5mm-thick gel samples were successfully obtained and found to have a density of 365 kg3. The high gas content was confirmed by ultrasound reflectivity measurements. The mean pore diameter, determined by optical and SEM measurements, was 131μm with a standard deviation of 57μm. Copyright © 2010 The Berkeley Electronic Press

Probing supramolecular protein assembly using fluorescent molecular rotors

We present a new optical approach for monitoring supramolecular assembly of proteins by following the fluorescence lifetime of environment-sensitive dyes termed Molecular Rotors (MR)

Mechanisms of microbubble mediated drug delivery

There is now a substantial literature demonstrating the potential of surfactant stabilised microbubbles as drug delivery agents; particularly in combination with therapeutic ultrasound. Microbubbles provide a means of encapsulating drugs to avoid interaction with healthy tissue