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Silk fibroin - characterization and chemical modification of a unique biomaterial for controlled release

Nultsch, Kira Helga Maria. Silk fibroin - characterization and chemical modification of a unique biomaterial for controlled release. 2018, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12910

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Abstract

Around 100 years ago, Paul Ehrlich postulated the “magic bullet”, a personalized and tailored drug that can hit the affected tissue like a bullet from a gun. Since then on a lot of research has been conducted to develop such “magic bullets”. To deliver a drug to the target location, usually a carrier/vehicle is needed (drug delivery system). Conventional ways to administer drugs are by tablets or parenterals, whereas the latter often suffers from high plasma concentration for a short time period, followed by a more or less fast decrease of the plasma concentration. Depending on the elimination constant, repeated drug administration can lead either to a diminished effect if the active ingredient is fast eliminated, or to side effects if the active ingredient cumulates. To control the release, local drug release might be considered with the advantage that systematic side effects can be reduced. As a result, local drug delivery systems gain more and more interest with the challenge to achieve a sustained release without impacting the surrounding healthy tissue. In order to achieve this controlled drug delivery and an optimal therapeutic effect, a lot of research has been carried out for targeted delivery with a controlled release rate. However, a drug delivery system has to meet several requirements, e.g. mechanical stability, controllable structure and degradation. Due to its extraordinary properties (e.g. mechanical strength, biocompatibility, biodegradability into non-toxic products, FDA-approved), silk fibroin (SF) has been in the focus of research since a long time, especially in terms of sustained release drug delivery systems. One of the major advantages of SF compared to other biomaterials is that it can be assembled into a variety of matrices (e.g. particles, foams, gels, electrospun mats) [1, 2].
The objective of the first study was to characterize silk fibroin in more detail. The focus was set on different purification processes of SF in order to efficiently remove sericin and a method to detect residual sericin was established. This is important to ensure biocompatibility since the combination of sericin and silk fibroin can cause allergic reactions. The degumming process significantly affected SF integrity, particularly mechanical strength and molecular weight distribution. These factors are crucial for the preparation of drug delivery systems, since they can influence the degradation rate of the drug delivery system and as a result, the release rate of the drug.
The second study aimed to investigate the release behaviour of differently charged macromolecular drugs from SF films. Since biologicals and nucleic acids (respectively nucleic acid/polymer complexes) are becoming an emerging field, the importance to understand the release behaviour of these macromolecular, charged compounds is growing. Therefore, differently charged, high molecular weight dextran derivatives, used as model drugs, were encapsulated into SF films and their release behaviour was studied. Additionally, the effect of SF purification process, with focus on degumming time, on drug release was elucidated. The release rate was found to be highly dependent on matrix properties, controllable via the purification process.
In the third part, silk fibroin films were chemically modified via copper (I)-catalyzed alkyne-azide cycloaddition (CuAAC) to further control drug release. The already existing, extraordinary features of silk fibroin can be enlarged by chemical modification, extending their range of applications. By varying the modification degree, the release was controlled, aiming a more pronounced sustained release, and additionally, the surface properties with regard to hydrophilicity were tuned.
Advisors:Imanidis, Georgios and Fischer, Dagmar
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Imanidis, Georgios
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12910
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (128 Seiten)
Language:English
Identification Number:
Last Modified:21 Dec 2018 05:30
Deposited On:20 Dec 2018 11:11

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