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- Status: Published
Description
Many therapeutics administered for some of the most devastating illnesses can be toxic and result in unwanted side effects. Recent developments have been made in an alternative treatment method, called gene therapy. Gene therapy has potential to rectify the genetic defects that cause a broad range of diseases. Many diseases, such as cancer, cystic fibrosis, and acquired immunodeficiency (AIDS) already have gene therapy protocols that are currently in clinical trials. Finding a non-toxic and efficient gene transfer method has been a challenge. Viral vectors are effective at transgene delivery however potential for insertion mutagenesis and activation of immune responses raises concern. For this reason, non-viral vectors have been investigated as a safer alternative to viral-mediated gene delivery. Non-viral vectors are also easy to prepare and scalable, but are limited by low transgene delivery efficacies and high cytotoxicity at effective therapeutic dosages. Thus, there is a need for a non-toxic non-viral vector with high transgene efficacies. In addition to the hurdles in finding a material for gene delivery, large-scale production of pharmaceutical grade DNA for gene therapy is needed. Current methods can be labor intensive, time consuming, and use toxic chemicals. For this reason, an efficient and safe method to collect DNA is needed. One material that is currently being explored is the hydrogel. Hydrogels are a useful subclass of biomaterials, with a wide variety of applications. This class of biomaterials can carry up to a thousand times their weight in water, and are biocompatible. At smaller dimensions, referred to as micro- and nanogels, they are very useful for many biomedical applications because of their size and ability to swell. Based on a previously synthesized hydrogel, and due to the advantages of smaller dimension in biomedical applications, we have synthesized aminoglycoside antibiotic based nanogels and microgels. Microgels and nanogels were synthesized following a ring opening polymerization of epoxide-containing crosslinkers and polyamine-containing monomers. The nanogels were screened for their cytocompatibilities and transfection efficacies, and were compared to polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Nanogels demonstrated minimal to no toxicity to the cell line used in the study even at high concentrations. Due to the emerging need for large-scale production of DNA, microgels were evaluated for their binding capacity to plasmid DNA. Future work with the aminoglycoside antibiotic-based nanogels and microgels developed in this study will involve optimization of nanogels and microgels to facilitate in better transgene delivery and plasmid DNA binding, respectively.
ContributorsMallik, Amrita Amy (Author) / Rege, Kaushal (Thesis advisor) / Dai, Lennore (Committee member) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
Environmentally responsive microgels have drawn significant attention due to their intrinsic ability to change volume in response to various external stimuli such as pH, temperature, osmotic pressure, or electric and magnetic fields. The extent of particle swelling is controlled by the nature of the polymer-solvent interaction. This thesis focuses on design and synthesis of environmentally responsive microgels and their composites, and encompasses methods of utilizing microgel systems in applications as vehicles for the adsorption, retention, and targeted delivery of chemical species. Furthermore, self-assembled microgel particles at ionic liquid (IL)-water interfaces demonstrate responsive colloidal lattice morphology. The thesis first reports on the fundamental aspects of synthesis, functionalization, and characteristic properties of multifunctional environmentally responsive microgels derived from poly(N-isopropylacrylamide) (PNIPAm) and other functional co-monomers. In particular, the uptake and release of active chemical species such as rheology modifiers into and from these ionic microgels is demonstrated. Moreover, a facile tunable method for the formation of organic-inorganic composites with Fe3O4 nanoparticles adsorbed and embedded within ionic microgel particles is explored. Additionally, the development of zwitterionic microgels (ZI-MG) is presented. These aqueous ZI-MG dispersions exhibit reversible parabolic swelling as a function of pH and display a minimum hydrodynamic diameter at a tunable isoelectric point (IEP). This study also elucidates the controlled uptake and release of surfactants from these particle systems. The extent of surfactant loading and the ensuing relative swelling/deswelling behaviors within the polymer networks are explained in terms of their binding interactions. The latter part of this thesis highlights the versatility of fluorescently labeled microgel particles as stabilizers for IL-water droplets. When the prepared particles form monolayers and equilibrate at the liquid-liquid interface, the colloidal lattice organization may re-order itself depending on the surface charge of these particles. Finally, it is shown that the spontaneously formed and densely packed layers of microgel particles can be employed for extraction applications, as the interface remains permeable to small active species.
ContributorsChen, Haobo (Author) / Dai, Lenore L (Committee member) / Chen, Kangping (Committee member) / Forzani, Erica (Committee member) / Lind, Mary Laura (Committee member) / Mu, Bin (Committee member) / Arizona State University (Publisher)
Created2015
Description
Monodispersed zwitterionic microgel (ZI-MG) particles that undergo an extensive, reversible change in volume in response to environmental stimuli such as pH and temperature were synthesized. These aqueous ZI-MG dispersions exhibited a minimum hydrodynamic diameter value at an adjustable isoelectric point(IEP). In addition, the study elucidates the controlled uptake and release of ionic and nonionic surfactants from these particle systems. The extent of surfactant loading and the ensuing relative swelling/deswelling behaviors within the colloidal polymer networks are explained in terms of their binding interactions.
ContributorsKelley, Morgan Taylor (Author) / Dai, Lenore L. (Thesis director) / Chen, Haobo (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05