Roffo, Felicia (2023) Impact of material engineering on stability of lipid-based nanoparticles and their application to microRNAs. [Tesi di dottorato]

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Abstract

This thesis aims to understand how the complexation of material, lipid and polymer influences the stability of the carrier, impacting on its performance at multiple levels. The interaction of these materials has been investigated in their processing, employing one step microfluidic process that enables control in a predictable manner the fluid interfaces to guide the formation and stabilize the hybrid lipid-polymer nanoparticle (LiPoNs). To gain further insight into the solvent interdiffusion and their spatial distribution along the device, a Comsol simulation of the convective-diffusive mixing taking place in the cHFF was computed. In a preliminary model, we have rationalized the effect of fluid confinement on nanoparticle formation, surpassing the concept of pure diffusion of solvents in describing their formation. The structural integrity of the final carrier and its cargo in different biological environments was investigated. We studied the role of material in mediating cellular interactions and the effective delivery of a stable cargo to the cells, going beyond the chemotherapeutic agents to more sensible molecules such as microRNAs. Furthermore, we investigated the impact of the NPs-cell interface on enabling or limiting the cell machinery at the single cell level.

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