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often observed in
fibrils, such as wild-type curli, play a
positive role in the yield characteristics of the material.
Other applications, which have not yet been found in nature,
can also be envisaged by directing the functional properties into
new areas. On such example is the suggested use of amyloid as a
depot for the formulation of long-acting drugs.
ex vivo
8
This is based on the
rationale that an amyloid forming drug takes the structural form of
a stable reservoir, containing only the peptide of interest, whereby
drug release is controlled from the fibril termini and the drug is
active upon release. The viability of this approach was explored
for a family of short- and long-acting analogues of gonadotropin-
releasing hormone (GnRH).
8
analysis showed that all of
the long-acting analogues formed fibrils that slowly released the
amyloid monomers. Further,
In vitro
subcutaneous administration
of a fibrillar sample was found to result in a longer duration of
action than its corresponding soluble counterpart. It is thought that
monomer release
in vivo
may be altered by binding components
from the host, such as glycosaminoglycans, that have the effect of
stabilizing amyloid fibrils, protecting them from degradation and
possibly reducing the potential immune response by covering
the fibrils. This would be of considerable practical benefit in
applications. The researchers also explored the potential pitfall in
attempting to utilize such a drug delivery system of cross-seeding,
using one of the long-acting GnRH analogues, and found no evidence
of cross-seeding either for wild-type GnRH or α-synuclein.
For applications within the human body, the issue of potential
toxicity of these functional fibrils will need to be addressed, as
indeed is the case for all new nanomaterials.
in vivo
22
Here it is important
to remember that it is not the material per se that is either toxic or
non-toxic but the material in concert with its local environment and
its kinetic evolution which need to be considered, understood, and
controlled.
10.6 
Conclusions
The rapid growth in the discovery of functional amyloid in recent
years should help to establish where and why this generic structure
is most likely to be found in a functional context. The diversity of
functions and organisms utilizing amyloid structures should help
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