Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study.

OBJECTIVE: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs. DESIGN: Prospective animal study. SETTING: Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia. SUBJECTS: Four weaned Border-Leicester/Suffolk lambs at 5 months of age. INTERVENTIONS: Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure. MEASUREMENTS AND MAIN RESULTS: Both the HYDRA and AeroNeb Go® produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 µm, range = 0.54-5.41µm) and the AeroNeb Go® (3.07 ± 1.56 µm, range = 0.86-10 µm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung. CONCLUSIONS: Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.

In vivo deposition study of a new generation nebuliser utilising hybrid resonant acoustic (HYDRA) technology.

Conventional nebulisation has the disadvantages of low aerosol output rate and potential damage to macromolecules due to high shear (jet nebulisation) or cavitation (ultrasonic nebulisation). HYDRA (HYbriD Resonant Acoustics) technology has been shown to overcome these problems by using a hybrid combination of surface and bulk sound waves to generate the aerosol droplets. We report the first in vivo human lung deposition study on such droplets. Twelve healthy adult subjects inhaled saline aerosols radiolabelled with technetium-99 m complexed with diethylene triamine penta-acetic acid (99mTc-DTPA). The distribution of the aerosolised droplets in the lungs was imaged by single photon emission computed tomography combined with low dose computed tomography (SPECT/CT). The volume median diameter and geometric standard deviation of the droplets were 1.32 ± 0.027 µm and 2.06 ± 0.040, respectively. The mean delivery efficiency from the nebuliser into the body was 51.2%. About 89.1 ± 4.3% and 2.3 ± 1.4% of the inhaled radiolabelled dose deposited in the lungs and oropharynx, respectively. The deposition was symmetrical and diffusive between the two lungs, with a mean penetration index of 0.82. Thus, the prototype HYDRA nebuliser showed excellent in vivo aerosol deposition performance, demonstrating its potential to be further developed for clinical applications.

Extensional viscosity of copper nanowire suspensions in an aqueous polymer solution.

Suspensions of copper nanowires are emerging as new electronic inks for next-generation flexible electronics. Using a novel surface acoustic wave driven extensional flow technique we are able to perform currently lacking analysis of these suspensions and their complex buffer. We observe extensional viscosities from 3 mPa s (1 mPa s shear viscosity) to 37.2 Pa s via changes in the suspension concentration, thus capturing low viscosities that have been historically very challenging to measure. These changes equate to an increase in the relative extensional viscosity of nearly 12,200 times at a volume fraction of just 0.027. We also find that interactions between the wires and the necessary polymer additive affect the rheology strongly. Polymer-induced elasticity shows a reduction as the buffer relaxation time falls from 819 to 59 µs above a critical particle concentration. The results and technique presented here should aid in the future formulation of these promising nanowire suspensions and their efficient application as inks and coatings.

Motility induced changes in viscosity of suspensions of swimming microbes in extensional flows.

Suspensions of motile cells are model systems for understanding the unique mechanical properties of living materials which often consist of ensembles of self-propelled particles. We present here a quantitative comparison of theory against experiment for the rheology of such suspensions in extensional flows. The influence of motility on viscosities of cell suspensions is studied using a novel acoustically-driven microfluidic capillary-breakup extensional rheometer. Motility increases the extensional viscosity of suspensions of algal pullers, but decreases it in the case of bacterial or sperm pushers. A recent model [Saintillan, Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2010, 81, 56307] for dilute active suspensions is extended to obtain predictions for higher concentrations, after independently obtaining parameters such as swimming speeds and diffusivities. We show that details of body and flagellar shape can significantly determine macroscale rheological behaviour.