Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 78

4.2.1 Growth Factors
Once a GF interacts with its receptor it leads to changes in gene expression
generating an integrated and multifaceted biological response on cells such
as chemotactic, mitogenic, morphogenic, apoptotic, metabolic effects or the
combination of several of these. 32,33
The effect of a GF in directing the phenotype of both stem and differen-
tiated cells depends on a variety of factors such as time of action, concen-
tration, micro-environmental cues besides the presence of other GFs. Small
amounts of a GF (picograms to nanograms) are needed to see an effect,
which is why regulation of GFs occurs at different levels from inhibition of
transcription to the degradation of the peptide. 33
When thinking of GF molecules for therapy it is important to take into
account that they are not conventional drugs. Herein we review some criteria
when designing a DDS for GFs:

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The identification of the key GFs for delivery in a particular application
should be based on an understanding of their biological developmental
processes, their characterization and whether they are available in large
quantities as recombinant proteins. 33
The GF or factors must target the chosen tissue when administered, and
side effects should be avoided 33 by using local delivery or functionali-
zation of the particles.
The loading capacity of the DDS that corresponds to the amount of
growth factor that can be included into the system should be assessed. 34
Often, fabrication of DDSs could cause degradation or inactivation of the
peptide, changes in its metabolic half-life and immunogenicity. The
strategies to preserve protein stability are based on an understanding of
the degradation mechanisms and the effect of changes in the storage
conditions and formulation conditions such as pH, ionic strength,
temperature, and buffer composition. 9,33,35 A profound knowledge of the
nature of the GF or factors, their degradation routes and micro-
environmental conditions in situ would help in the choice of the most
accurate DDS fabrication method. Adding carriers that contain the GF
also help to preserve their bioactivity as well as their appropriate release. 34
The release profile of the GF from the DDS should be controlled tempo-
rally and spatially, allowing the appropriate dose of GF to reach the cells
over a given period of time. DDS should be able to retain the GF or factors
at the target tissue to see an effect. The range of effective concentration
thresholds has to be considered. Spatial localization of the signaling
molecule allows their direct effect within the tissue to be followed up. 9,34
The binding anity defines how tightly the GF binds to the DDS; this
must be suciently low to allow release, but high enough to prevent
uncontrolled release. 34
To be economically viable, the DDS must be easy to manufacture and
handle, and be cost-competitive.

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