Chemical and Biomolecular Engineering - Theses
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ItemAssembly of therapeutic carriers for sustained delivery of neurotrophins to the cochlea( 2013)Gradual degeneration of auditory neurons following sensorineural hearing loss is normally caused by a depleted supply of neurotrophins, as a result of the death of the cochlear hair cells, which secrete the signaling proteins. Animal studies show that the neurodegeneration could be prevented by exogenous administration of neurotrophins, which include brain derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), nerve growth factor (NGF) and neurotrophin -3 (NT-3). Optimum therapeutic benefit, however, requires continuous administration for a prolonged period. Although many novel delivery strategies (e.g. gene therapy, mini osmotic pumps and polymer hydrogels) have been previously proposed, none has been utilized at the clinical stage due to concerns about safety, cost and insufficient protein release. The primary focus of this thesis is the assembly and characterization of therapeutic carriers for the sustained delivery of neurotrophins to the cochlea. The study investigated two different carriers, namely capsosomes and calcium carbonate (CaCO3) supraparticles, by characterizing their loading capacities, as well as their long-term release kinetics in simulated physiological conditions, using lysozyme as a model protein and the BDNF. The capsosomes were prepared by incorporating liposomal compartments within hydrogel capsules using the layer by layer (LBL) assembly method, while the CaCO3 supraparticles were prepared by the evaporation initiated self-assembly of mesoporous calcium carbonates particles. The release of the proteins from the capsosomes was mainly dependent upon the composition of the liposomal compartments, while particles size and porosity governed the release from the supraparticles.