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Title: Chitosan nanoparticles by ionic coacervation for protein release and gene transfection
Author: Wang, T.
Awarding Body: Queens -Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Abstract:
The Ph.D. dissertation focuses on providing in depth understanding and scientific Iaiowledge usable to realize the potential of chitosan nanoparticles as protein release vehicles and non-viral gene carriers for phannaceutical applications. The preparation ofthe nanoparticles was based on the ability of chitosan to undergo a liquid-gel transition due to ionic interaction with polyanion, such as tripolyphosphate (TPP..). The chitosan-TPP nanoparticles had a particle size range 100-250 nm, positive zeta potential around +28-+52 mV ·and exhibited a high positive surface charge across a wide pH range. The particular imaging analysis of the nanoparticles morphologies revealed that the nanoparticles possessed typical characterization of polyhedrons, indicating an analogy to crystallization mechanism during the nanoparticles formation and growth process. The BSA-Ioaded chitosan nanoparticles formed by both incorporation and incubation methods were in the size range of200-700 nm, and exhibited a positive zeta potential +43-+56 mY. BSA encapsulation efficiency varied from 39 to 88 wt%. Detailed sequential time frame TEM imaging of morphological changes of the nanoparticles showed a swelling and particle degradation process. BSA release showed a typical initial burst within 6 hours followed by an extended slow release. Higher gene transfection efficiency with DNA-loaded chitosan nanoparticles was optimized to reach a peak value of20.2% at chitosan concentration 0.2 mg/ml, which is 5.4% higher than chitosan-DNA complexes. Further analysis of life cycle of gene expression of DNA-loaded chitosan nanoparticles was detectable at 24 days with its compact structure and multiple ionic crosslink, provided better shielding and protection of DNA molecules from enzymatic degradation. .It demonstrates that chitosan-TPP nanoparticles can be a versatile carrier for protein release and gene transfection, and polyanionic crosslink TPP of polycationic chitosan molecules offers simple preparation. conditions and clear processing windows for manipulation of physiochemical properties, especially particle size and surface charge.
Supervisor: Not available Sponsor: Not available
Qualification Name: Queens -Belfast, 2008 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.487466  DOI: Not available
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