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978-3-8439-3560-9, Reihe Pharmazeutische Technologie
Katharina Jasmin Geh
Gelatine Nanoparticles as Immunomodulatory Drug Delivery System - Advanced Production Processes and Clinical Trials
211 Seiten, Dissertation Ludwig-Maximilians-Universität München (2018), Hardcover, A5
Nanoparticles are intensively researched as drug delivery systems since the 1970s. Amongst a variety of starting materials for nanoparticles, gelatine has proven to be versatile due to its biodegradability, biocompatibility and low immunogenicity. Furthermore, gelatine provides several functional groups, which allow cross-linking and surface modifications of gelatine nanoparticles (GNPs).
Besides different small molecules, GNPs were sucessfully investigated for their potential as drug delivery system for macromolecules, such as therapeutic proteins or nucleic acids. Several studies showed the effective treatment of allergic diseases, such as equine recurrent airway obstruction, by cytosine phosphote guanosine oligodeoxynucleotides (CpG ODNs) bound to gelatine nanoparticles. Following recognition of the innate immune system via toll-like receptor 9 (TLR9), CpG ODNs are able to restore the disrupted balance between Th1 and Th2 immune response in allergy driven diseases. Furthermore, regulatory T cells (Treg), which control T helper cell reactions in general, can be activated. GNPs are able to protect these sensitive oligodeoxynucleotides from degradation and enhance their cellular uptake by antigen presenting cells due to their particle sizes similar to microorganisms.
The work presented in this thesis focused on the optimisation of the preparation process of gelatine nanoparticles and subsequent scale up into gram scale.
Additionally, the long-term stabilisation of CpG ODN-loaded GNPs via lyophilisation was demonstrated. Further insights into the understanding of pertaining lyophilisation processes and formulations were gained.
Moreover, sterilisation of loaded and unloaded GNPs either by gamma irraditaion or steam sterilisation was established.
Finally, a preliminary clinical evaluation of CpG ODN-loaded GNPs in canine atopic dermatitis is described.