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The shape of drug delivery
04-09-2007
by Randall C Willis  |  Email the author
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PHILADELPHIA—One of the inherent challenges of using microspheres and nanoparticles as drug delivery vehicles is their relatively rapid clearance from the body, which can occur within days or hours. Taking a cue from viral pathogens, researchers at the University of Pennsylvania and Rutgers University examined the impact of changing the nanoparticle shape from spherical to filamentous on biological half-life.
 
As they described in Nature Nanotechnology, the researchers constructed "filomicelles" comprised copolymers of hydrophilic PEG and hydrophobic polyethylethylene (inert) or polycaprolactone (biodegradable). By changing the hydrophilic/hydrophobic polymer ratios, the researchers could vary the dimensions of the filomicelles. Injecting the filomicelles into tail veins of rats and mice, they used fluorescence imaging of blood samples to monitor in vivo circulation.
 
The researchers found that filomicelles were thoroughly dispersed and sustained in the circulatory system within the first couple of minutes. They noted that whereas PEGylated stealth spheres were completely cleared from the blood stream within a day or two, a portion of the filomicelles remained for up to a week. They also noted that longer filomicelles, approximating the size of a blood cell, tended to last longer than short filomicelles but that these were also prone to fragmentation, either by shear forces or chemical hydrolysis.
 
In static culture, the researchers noted that the filomicelles were rapidly taken up by activated phagocytes but this process was diminished when the cells and filomicelles were exposed to a steady fluid flow. The researchers then tested the filomicelles for their ability to deliver the anticancer drug paclitaxel in vivo to tumor-bearing nude mice and noted that filomicelle delivery mimicked free drug delivery but was a significant improvement over recently reported results in clinical trials using spherical PEG micelles.
 
The findings suggest that filomicelles represent a potentially more effective way to deliver drugs in vivo, but more importantly, offer insights on the impact of shape on nanoparticle attachment to and uptake by cells in vivo and in vitro.

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