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Imaging Therapeutic Proteins in Gelatin for Controlled Drug
Release
Nilda
Juan Serrano, MS in Materials Science, May 2005
In response to
an event disrupting bone function, such as disease or trauma,
proteins are secreted to initiate healing. Disease and other factors
can diminish the ability of bone to self-repair. Therefore,
augmentation through the use of artificial bone may be required. The
addition of therapeutic proteins, or growth factors, to engineered
bone constructs is believed to elucidate a more natural response at
the defect site and to decrease healing time.
Drug delivery
vehicles must be carefully engineered in order to optimize the dose
and dose rate and these parameters must be monitored over time and
space. One technique used to measure the pharmacokinetics of growth
factors is radioactive labeling. However, this only yields an
average value over the sample; it does not provide a 3D
description. The radioactivity of the label adds further
complications. Our results show that labeled, model proteins can be
imaged in 3D using x-ray microcomputed tomography.
Polymer
microspheres, engineered to mimic the natural release of growth
factor, were loaded with labeled protein and incorporated into a
hydrogel matrix. The protein was labeled with either non-radioactive
iodine or gold nanoparticles, both of which provide x-ray absorption
contrast. Using synchrotron radiation at the
Advanced Photon Source at
Argonne National Laboratory, we imaged hydrogel samples (Figure 1).
Preliminary results demonstrate the feasibility of imaging the
proteins in this manner and that for the same concentration the gold
label provides better contrast. This technique will allow us to
create a 3D representation of the pharmacokinetics, rapidly, and
without radioactive tracers. Results will have significant impact on
clinical design of bone implants.
Gelatin sheet
with Au-labeled protein in microspheres |
Microspheres
containing Au-labeled soybean tripsin inhibitor (STI) |
3D image of dried
gelatin sample |
 |
 |
 |
Figure 1. Cross-sectional
micro-ct images of (left) a gelatin sheet injected with
microspheres loaded with the Au-labeled model protein, soybean
tripsin inhibitor (STI), and (middle) microspheres containing
Au-labeled STI. Insets show enlargements of the regions indicated
by the black arrow. Ring
artifacts are shown in near the white arrow in left image.
Note the concentrated bright spots in each image,
indicative of a higher attenuation, and therefore the presence of
the gold nanoparticles.
Iodinated samples showed similar results.
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