Silk Biomaterials for Controlled Drug Delivery.
Pritchard, Eleanor.
2011
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Abstract: Despite
the multitude of applications, no system currently exists for controllable, sustained,
long-term drug delivery via fully degradable implants. To address this need, polymeric
systems have been studied and while there are a number of biomaterials available for
drug delivery devices, purified silk fibroin protein is a unique material particularly
well suited to controlled release ... read moreapplications. Implants derived from silk exhibit the
requisite biocompatibility and degradation profile for implantable applications, but
also possess the necessary material properties to provide a sufficient diffusion
barriers (even for small molecule drugs) and highly-controllable material features that
can in turn be used to precisely tailor drug release behavior. Studies have suggested
that a particular desired release profile adapted to the target drug delivery
application can be obtained by varying polymer coating formulation and processing
parameters, but the systematic characterization of these effects necessary to achieve
tight control has never been undertaken. Release of the small molecule adenosine from a
variety of silk-based drug delivery systems was examined to correlate fundamental
relationships between material features (e.g., processing conditions, crystallinity,
degumming time, layer thickness, etc.) and resulting release kinetics. Characterizing
and modeling these effects led to development of an integrated model that incorporated
multiple control points that could be modulated to achieve specific target release
profiles. The predictive accuracy of the model was confirmed by comparing theoretical
release predictions to experimental release behavior. Degradation also played a role in
drug release both in cases of freely diffusible drugs and for drugs bound to the silk
matrix. Degumming time, film fabrication process and coating thickness impacted
degradation of the silk carriers and release kinetics. Strategies to control local
proteolytic degradation via proteinase inhibitors and proteolytic enzymes were
demonstrated. Silk drug delivery implants have significant potential clinical
applications due to the features above, including treatment of neurological disorders,
stabilization and delivery of antibiotics and incorporation of signaling molecules into
tissue engineering scaffolds. These fundamental and application-driven in vitro and in
vivo studies showed that hydrophobic, hydrophilic, small and large molecule drugs can be
entrapped and released from silk-based devices with tight control of the release
kinetics through manipulation of the implant processing and material
properties.
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Sergio Fantini, Catherine Kuo, James Schwob, and Anthony Barry.
Keyword: Biomedical Engineering.read less - ID:
- 9c67wz92n
- Component ID:
- tufts:20975
- To Cite:
- TARC Citation Guide EndNote
