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<b><span style="font-size:18.0pt;font-family:"Arial",sans-serif;color:#C8102E">Development, Characterization, and Performance Evaluation of Nanoliposomes with Tunable Rigidity for Delivery Applications </span></b><span style="font-size:18.0pt;color:#C8102E"><o:p></o:p></span></p>
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<strong><span style="font-size:13.5pt;font-family:"Calibri",sans-serif">Fereshteh Mirab</span></strong><span style="font-size:13.5pt"><o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif">November 11, 2022; 1:00 PM - 3:00 PM (CST)<br>
Location: SERC 2028<o:p></o:p></span></p>
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<strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif">Committee Co-Chairs:</span></strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif"><o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif">Dmitri Litvinov, Ph.D.
<span style="background:white">|</span> Sheereen Majd, Ph.D.<o:p></o:p></span></p>
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<strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif">Committee Members:</span></strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif"><br>
Chandra Mohan, Ph.D. | Vijaykrishna Raghunathan, Ph.D. | Tianfu Wu, Ph.D.<o:p></o:p></span></p>
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<strong><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E">Abstract</span></strong><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E"><o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black">Nanoparticle-based delivery systems have emerged as a promising platform for delivery of therapeutics and diagnostics to specific sites in the body. To date, some of the nanocarrier’s
physicochemical properties including size, shape, and surface chemistry, are well established as key factors for their delivery performance. Recent studies have suggested that the mechanical properties of nanoparticles can also influence their performance
as delivery carriers. This rather new aspect of nanoparticles that may provide new avenues for improving drug delivery, remains unexplored in nanoliposomes -one of the most successful delivery carriers developed to date. The goal of this doctoral project is
to develop nanoliposomes with tunable rigidity, characterize their physical and mechanical properties, and investigate the role of nanoliposomes’ rigidity in their cellular interactions to provide an improved understanding of the significance of nanoparticles’
mechanics for their delivery applications. One focus of this study is development and characterization of nanoliposomes with various rigidity levels. To enable tuning the liposomal mechanical properties without changing their other physicochemical properties,
we prepared nanoliposomes with cores of hydrogels of various compositions and thus, mechanics. Two biocompatible and biodegradable hydrogels, poly(ethylene glycol) diacrylate (PEGDA) and alginate, were used as the liposome core at various compositions, and
the resultant gel-core nanoliposomes (GNLs) were characterized for size distribution, morphology, and surface potential. Next, the mechanical properties of the resultant GNLs were assessed. To this end, we initially evaluated the mechanical properties of bulk
hydrogels at different compositions using rheological measurements and compression testing to determine hydrogels’ elastic modulus as a function of their composition. Subsequently, we precisely assessed the mechanical properties of the GNLs in nanoscale using
atomic force microscopy (AFM). Upon careful optimization of these experiments, we successfully imaged the GNLs via AFM and determined their Young’s modulus by single particle indentation. Ultimately, we focus on the effect of particles’ rigidity on their cellular
interactions including cellular uptake using different cell types (glioblastoma tumor cells, brain endothelial cells, astrocytes, and spleen immune cells) as well as their transport across an in vitro blood-brain-barrier (BBB) model. Briefly, nanoliposomes
with more rigidity demonstrated higher cellular uptake compared to their softer counterparts. However, the ability of GNLs to cross the BBB was not affected by their rigidity. Similarly, exocytosis assay of GNLs on endothelial cells indicated this rigidity
independency. Further, the effect of particles’ elasticity on their cellular interaction on immune cells was investigated. Lastly, ligand targeting of nanoliposomes was examined using folate cap lipids. The findings of this research can lead to improved nanotherapeutics’
design for enhanced delivery to diseased tissues. discussed.</span><span style="font-size:10.5pt;font-family:"Arial",sans-serif"><o:p></o:p></span></p>
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