Nydeia Wright-Bolden, Ph.D. (2011)
Dissertation Topic: Synthesis of Magnetic Nanoparticles for Drug
Major Professor: Dr. Vijaya Rangari, Professor of Materials Science & Engineering
M.S.: Chemistry, Tuskegee
B.S.: Chemistry, University of Alabama –
Employment: Eglin Air Force Base, Orange Beach, FL
The motivation for this study is to develop magnetic nanoparticles as drug carrier systems. It is anticipated that the presence of these magnetic nanoparticles will increase the efficacy of drug delivery by directing the drugs to the desired location through interactions with an external magnetic field. The aided journey to the selected site may decrease the amount of drug affecting healthy cells by restricting cancer drugs to a specific location. Cancer drugs are reasonably effective against tumorous cells; however, there is no mechanism to prevent these drugs from attacking viable cells. It is possible that an external magnetic field may be used to direct drugs to a targeted site for release without affecting viable cells. The main challenges in these systems are preservation of magnetic properties, biocompatibility, aqueous stability, drug loading capacity, and specific release profiles.
In this study, four types of superparamagnetic iron oxide nanoparticles were synthesized. These particles were produced via sonochemistry, using two types of iron precursors (iron pentacarbonyl and iron (II) acetate) with various surfactants and solvents. The precursor solutions were irradiated with a high intensity ultrasonic horn for 3 hours, followed by additional heat treatments as needed. Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), Mossbauer spectra, and magnetization analyses were carried out. It was found that magnetic saturation (Ms), degree of crystallinity, and crystal structures were varied by varying the iron precursor, surfactants, and solvents. Among the four iron oxide nanoparticles synthesized, uncoated particles produced from iron acetate were chosen for encapsulation with Paclitaxel. The particles are determined to be Fe3O4, highly super paramagnetic (SPM), crystalline, ~10nm, and have minimal effects on cell viability. The as-prepared magnetite nanoparticles were initially coated with oleic acid and finally encapsulated with Paclitaxel in PLGA. Drug loading was carried out by a water-in-oil emulsion. The oil phase contained the drug, oleic acid coated iron oxide, and PLGA. These magnetic drug loaded microspheres were characterized by SEM and UV-vis. Magnetite and Paclitaxel were found to be adequately encapsulated in PLGA and to contain ~37µg/ml of drug. In vitro MTS assays were conducted to test the drug efficiency against tumor inhibition growth. Within the first 24 hours post incubation, low concentrations (0.01 µM) of co-encapsulated Paclitaxel and magnetite were shown to have a significant effect on both 4T1 and MCF 7 Breast Cancer Cell. In both cancer cell lines, viability was reduced to ~25%.
This work is the first of many steps in developing a magnetic drug delivery system capable of delivering hydrophobic cancer drugs such as Pacliatxel to a specific site with more accuracy and less toxicity than some current methods. The capability of this system is successfully demonstrated through its ability to maintain, attract, and release the drug. We have successfully synthesized magnetic nanoparticles that are suitable in size, toxicity, and magnetic strength. Further in vivo studies are needed to determine the efficiency of these co-encapsulated drug and magnetite loaded particles.