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Amphiphilic Polymer Assemblies Responsive To Chemical, Physical, And Biological Stimuli

Abstract
The applications of stimuli responsive materials have tremendously increased over the past decade. In particular, these materials can potentially be used for improving the selectivity and efficiency of delivering a payload (drug) in drug delivery applications. This thesis discusses the design and synthesis of amphiphilic polymers which can respond to chemical, physical, and biological stimuli. We have synthesized a novel amphiphilic block copolymer which can form micellar assemblies in aqueous medium and respond to multiple stimuli; viz physical (temperarure) and chemical (pH, DTT and gluthathione). This amphiphilic block copolymer is sensitive not only to a single stimulus, but also to the simultaneous presence of multiple stimuli. This system provides a unique opportunity to fine tune the release kinetics of the encapsulated hydrophobic guest molecules. Besides designing polymeric systems responsive to chemical and physical stimuli, we were also interested in systems responsive to biological stimuli, since they can directly respond to the primary imbalances in biological functions instead of a secondary change such as pH, or redox potential characteristics. Amphiphilic polymers designed earlier in the group with -COOH as the hydrophilic group are known to provide micellar assemblies in water. The charged exterior (-COO - ) of the micellar assemblies was used to disrupt protein-protein interaction. To further investigate if these polymeric micelles can be made responsive to proteins, we have studied the binding event of a ligand (pendant on the polymer chain) with the protein. Block copolymers and random copolymers functionalized with specific ligands were used as model systems to understand the interaction of polymers with proteins. We established that block copolymers provide better binding with proteins compared to random copolymers, possibly due to the higher effective molarity of ligands present in the former than the latter. Amphiphilic biaryl dendrimers decorated with ligands at different locations were also studied. We established that ligands present in at any layer of the dendron are equally available for binding with protein. Amphiphilic homopolymer and amphiphilic biaryl dendrimer were found to be the potential candidates for drug delivery applications by using proteins as the trigger to disassemble the micelles.
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campus
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dissertation
Date
2010-02-01
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