MICROENCAPSULATION AND PHARMACOLOGICAL TEST OF THERAPEUTIC CELLS

Micro-pharmaceutical factories are polymeric microcapsules, containing genetically modified cells, that achieve a sustained release of a chemotherapeutic factor, prior minimally-invasive in situ implant and systemic administration of the pro-drug.[1] In the past years this strategy has made its way through drug delivery systems as promising, universally applicable, tool for the treatment of different disease, allowing a localised sustained therapy, thus preventing important side effects. [2, 3, 4] To enable the application of this strategy, it is required a system that allows an high density cell encapsulation, to provide a therapeutic dose, and whose fabrication is simple, reproducible and fast. The THERACAGE project stems from addressing those needs: this thesis will show the application of novel materials and techniques for high density cells encapsulation in micro particles through spontaneous emergence in a synthetic microfluidic paper (i.e., scaffold with interlocked micro-pillars), employing new generation thiol-ene based polymers for both particle design and manufacturing process. The first chapter describes objectives and structure of the thesis in detail. The subsequent ones (chapter two and three) provide the bio-medical background from which this project arises ad the description of the project itself. The following ones (chapters four and five) will show the scaffolds manufacturing and surface chemistry modification to achieve a homogeneous and stable droplet formation. Then (chapter six), it will be illustrated the development of the cell encapsulation technique to obtain an high cell density within the particles. Afterwards, the in vitro testing of the cells pharmacological effectiveness (chapter seven) and the in vitro viability assays performed to evaluate bio-compatibility of the materials and the procedures(Chapter eight) will be reported. Last but not least, conclusions and future developments will be adduced in the final chapter.