Design of monoaxial and coaxial Electrospun membranes for Biomedical applications

Abstract

According to the Institute for Health Metrics and Evaluation, cancer is a disease that each year causes above 17% of all global deaths (2017). Currently, the most used therapies are generally administrated orally or via injection. However, topical systems, differently from the traditional ones, can guarantee a way slower release of drugs in the biological environment that can be delivered directly to the zone of interest, providing less invasive treatment with fewer side effects. In this scenario, the present Ph.D. thesis aims to develop cutting-edge nanofibrous materials obtained through the electrospinning process designed for application in the biomedical field, in particular for cancer treatment. This process allows producing innovative drug delivery systems with peculiar morphology that can well mimic the structures of the human tissue (scaffolds). For this reason, they are particularly interesting for post-surgical cancer treatments. The present research is focused mainly on biocompatible and biodegradable polymers, to have no negative immune response by the system. Natural and synthetic biopolymer present significantly different properties, such as mechanical ones, biocompatibility, etc. Thus, the research has explored how the use of different process configurations (uniaxial electrospinning and coaxial electrospinning) affects the thermal, structural, and mechanical properties of the natural-synthetic biopolymer electrospun systems. Two types of fillers have been loaded in the electrospun systems: nanoparticles and active molecules. The first part of the performed research deals with the use of functionalized magnetic nanoparticles included in nanofibrous systems and the strategy of obtaining efficient dispersion of nanoparticles in polymeric nanofibers by enhancing the compatibility between the filler and the matrix. Relevant results have been obtained controlling the morphology and the thermal and mechanical properties. Antitumoral tests have shown highly promising results against several types of skin cancers. The second part of the activity involved two different approaches: on the one hand, the use of commercial chemotherapeutics (Dacarbazine), the drug used in the treatment of melanoma; on the other hand, the use of non-commercial complexes, ad hoc synthesized. The nanofibrous systems loaded with synthetic antitumoral metal complexes have shown outstanding activity against some very aggressive skin cancer. The systems have been investigated to understand how the affinity between the filler and the matrix affects the location of the active substance in nanofibrous systems, determining noticeable effects on the morphology and the drug release mechanism. Further investigations have been performed through a coaxial electrospinning process, which allows for obtaining bilayer nanofibers. The performed research highlighted that, by using a coaxial process, it is possible to control the release kinetics of the active substance. Furthermore, by selecting the chemical nature of the external and internal nature of the polymers of the coaxial nanofiber and the processing parameters appropriately, it is possible also to enhance the material's performance in terms of biocompatibility and mechanical performance. The coaxial configuration also allows for designing multistep release processes through a single biomedical device. [edited by Author]