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Abstract:
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Our ability to precisely manipulate size , shape , and composition of nanoscale carriers is essential for controlling their in -vivo transport , biodistribution , and drug release mechanism . Shape -specific , "smart" nanoparticles that deliver drugs or imaging agents to target tissues primarily in response to disease -specific or physiological signals could significantly improve therapeutic care of complex diseases . Current methods in nanoparticle synthesis do not allow such simultaneous control over particle size , shape , and environmentally -triggered drug release , especially at the sub -100 nm range . In this dissertation , we discuss the development of high -throughput nanofabrication techniques using synthetic and biological macromers (peptides ) to produce highly monodisperse nanoparticles , as well as enzymatically -triggered nanoparticles , of precise sizes and shapes . We evaluated thermal nanoimprint lithography (ThNIL ) and step and flash imprint lithography (SFIL ) as two possible fabrication techniques . We successfully employed ThNIL and SFIL for fabricating nanoparticles and have extensively characterized the SFIL fabrication process , as well as the properties of the imprinted biopolymers . Particles as small as 50 nm were fabricated on silicon wafers and harvested directly into aqueous buffer using a biocompatible , one -step release technique . These methods provide a novel way to fabricate biocompatible nanoparticles with precise size and geometry . Furthermore , we developed an enzyme -degradable material system and demonstrated successful encapsulation and enzyme -triggered release of antibodies and nucleic acids from these imprinted nanoparticles ; thus providing a potential means for disease -controlled delivery of biomolecules . Finally , we evaluated the bioactivity of the encapsulated therapeutics in -vitro . The development of the SFIL method for fabrication of biocompatible nanocarriers has great potential in the drug delivery field for its ability to create monodisperse particles of pre -designed geometry and size , and to incorporate stimulus -responsive release mechanisms . This research provides the potential to broaden the study of how particle size and shape affect the biodistribution of drugs within the body . |