Master's Defense: Noran Bassam Galal
Solid-state characterization of nano-embedded microparticles for pulmonary drug delivery
In this study, a drug delivery system, designed for pulmonary delivery of the monoclonal antibody Tocilizumab (TCZ), was synthesized and investigated. TCZ is a drug used against the interleukin-6 (IL-6) receptor, a main target against lung inflammation. To this end, poly(lactic-co-glycolide) (PLGA) nanoparticles were synthesized and functionalized with the polymers chitosan and Pluronic F127, and lastly TCZ was adsorbed to the surface. The individual constituents and the nanoparticle formulations were investigated with the aim of elucidating their physicochemical and structural properties, identifying if and how the constituents interact with one other, and verifying the cellular changes that occur due to the interaction of the drug with epithelial cells. Solid-state characterization of the nanoparticles, layer by layer, as well as the individual substances, were performed using Dynamic Light Scattering (DLS) and Zeta-(-potential, synchrotron Small Angle X-ray Scattering (SAXS), and Raman Spectroscopy and imaging. From the DLS and Zeta-potential results, we observed a wide size distribution of the nanoparticles, while based on the Raman images it was possible to get insight into the distribution of the components. Additionally, based on soft X-ray imaging analysis of A459 epithelial cells treated with the nanoparticles (with and without TCZ), the spatial distribution of lipid bodies and how they change in response to the nanoparticles was quantified. From the morphological assessments of cells treated with nanoparticles, either with or without TCZ, it was possible to observe differences between the cells, suggesting that the response upon cellular uptake is different. By performing segmentation of the X-ray images, it was possible to observe a shift in greyscale value and diameter distributions, which corroborates with the morphological changes.