ABSTRACTSYNTHESIS AND CHARACTERIZATION OF POLYMERIC AND INORGANICMATERIALS FOR BIOMEDICAL APPLICATIONSByGeorgina Annette ComiskeyThe need of safe biodegradable materials for drug delivery has been anincreasing demand. Polylactide is a biodegradable and bioresorbable polyester. Polylactide has the disadvantage of hydrophobicity and little functionality. Scientists have taken on the task of modifying polylactide to overcome its shortcomings while retaining its good properties. Herein, we explore the synthesis of substituted polylactides and their applications. We formed stereocomplexes of isotactic poly(isopropyl glycolide), a semicrystalline polyester. Stereocomplexes will have different thermal and crystallinity properties different from the homopolymers. We also explored the modification of poly(propargyl glycolide) (PPGL) via click chemistry and further crosslinking of PPGL clicked with PEG chains using a simple alkyl diazide or a diazide containing a disulfide bond to obtain reductively degradable PPGL nanoparticles. We compared the reductive degradation of the two types of nanoparticles obtained. Using click chemistry, we modified PPGL with azide ligands containing various functional groups, which were then crosslinked. We tested the interaction of the various surface functional groups with a cell membrane lipid bilayer mimic. Similarly, we synthesized reductively degradable PPGL clicked with amines and we assessed their use as siRNA delivery vehicles. We found out that these polymeric siRNA delivery vehicles were inefficient. In order to elucidate the reasons of the unsuccessful results of the previous attempt to deliver siRNA, we turned to surface modified silica nanoparticles containing dextran, which are very efficient siRNA delivery vehicles capable of triggering silencing of EGFP in human lung carcinoma cells without causing toxicity. We attempted to elucidate why these nanoparticles had such great silencing efficiency.
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