Ionic Copolymer-Magnetite Complexes for Magnetic Resonance Imaging and Drug Delivery
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This thesis is focused on the design, synthesis and characterization of magnetite-ionic copolymer complexes as nanocarriers for drug delivery and magnetic resonance imaging. The polymers included phosphonate and carboxylate-containing graft and block copolymers. Oleic-acid coated magnetite nanoparticles (8-nm and 16-nm diameters) were investigated. Cisplatin and carboplatin were used as sample drugs. The potentials of the magnetite-ionomer complexes as dual drug delivery carriers and magnetic resonance imaging agents were evaluated. An acrylate-functional poly(ethylene oxide) macromonomer and hexyl (and propyl) ammonium bisphosphonate methacrylate monomers were synthesized. Conventional free radical copolymerizations were conducted to synthesize the graft copolymers. The acrylate-functional poly(ethylene oxide) macromonomer was also used to form graft copolymers with tert-butyl acrylate. Block ionomers containing poly(tert-butyl acrylate) were synthesized via atom transfer radical polymerization, then the tert-butyl groups were removed to afford anions. All the monomers and polymers were characterized by 1H NMR to confirm their structures and assess their compositions. Phosphonate-containing polymers were also characterized by 31P NMR. Magnetite nanoparticles (8-nm diameter) were synthesized by reducing Fe(acac)3 with benzyl alcohol. The 16-nm diameter magnetite was synthesized by thermal decomposition of an iron oleate precursor in trioctylamine as a high-boiling solvent. The iron-oleate precursor was synthesized with iron (III) chloride hexahydrate and sodium oleate with mixed solvents. TEM images of the magnetite were obtained. Magnetite-ionomer complexes were synthesized by binding a portion of the anions (carboxylate or phosphonate) on the copolymers onto the surfaces the magnetite. The remainder of the anions was used to bind with cisplatin and carboplatin via chelation. Physicochemical properties of the complexes were measured by dynamic light scattering. All the complexes with different polymers and magnetite nanoparticles displayed relatively uniform sizes and good size distributions. The magnetite-ionomer complexes displayed good colloidal stabilities in simulated physiological conditions for at least 24 hours. Those graft and block copolymer-magnetite complexes may be good candidates as drug carriers for delivery applications. After cisplatin and carboplatin loading, the sizes of the complexes increased slightly and the zeta potential decreased slightly, which indicated that the loadings were successful. Minimal loss of iron was found, signaling that the binding strengths between the magnetite and the anions of the graft copolymers were strong. 8.7 wt% of platinum was found in the cisplatin loaded complexes and 6.9% in the carboplatin loaded complexes. The results indicated that the magnetite-graft ionomer complexes were capable of loading drugs. Drug release studies were performed at pH 4.6 and 7.4 to mimick endosomal conditions and the physiological environment. Sustained release of drugs was observed. This further indicated the potential for using the magnetite-ionomer complexes as drug carriers. Transverse relaxivities of the magnetite-ionomer complexes with and without drugs were measured and compared to a commercial T2-weighted iron MRI contrast agent-Feridex®. All the complexes had higher relaxivities compared to Feridex®. Thus, the magnetite-ionomer complexes are promising candidates for dual magnetic resonance imaging and drug delivery.Moreover, the aqueous dispersion of the complexes was found to heat upon exposure to an AC magnetic field, thus potentially allowing heat-induced drug release.
- Masters Theses