A Master of Science thesis in Chemical Engineering by Mihad Ibrahim entitled, "Anti-cancer Drug Delivery Using Metal Organic Frameworks (MOFs) and Ultrasound.," submitted in May 2016. Thesis advisor is Dr. Ghaleb Al Husseini and thesis co-advisor is Dr. Rana Sabouni. Soft and hard copy available.
Cancer is defined as the uncontrolled growth of abnormal cells. Although billions of dollars have been spent on cancer research to develop its treatments, cancer still remains a major illness for mankind, partly due to the drawbacks of these treatments. In an attempt to address the shortcomings of conventional chemotherapy (low targeting specificity, severe side effects and poor pharmacokinetics), anti-cancer drug delivery systems are being extensively researched using various nanocarriers including liposomes, micelles, polyelectrolyte capsules and others. Among the recent nanoparticles investigated as drug delivery vehicles are metal organic frameworks which are defined as porous hybrid polymers that consist of metal clusters and organic ligands. They have certain features that promote their use as drug carriers. First, they are nontoxic and have the ability to carry high loads of the drug. Also, their sizes are suitable to control in vivo and in vitro drug release. In this thesis, two new metal organic frameworks were prepared from iron nitrate and 2,6 naphthalenedicarboxylic acid. The first metal organic framework (Fe-NDC-M) was synthesized in a microwave oven, while the second (Fe-NDC-O) was prepared in an electrical conventional oven. Both were characterized using X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray and Fourier transform infrared spectroscopy techniques. Then, they were used to load calcein disodium salt (a model drug mimicking the anti-neoplastic agent doxorubicin). Both particles showed high loading efficiencies (greater than 98%). The release kinetics of the model drug in neutral phosphate buffered saline were investigated with and without acoustic irradiation. Without ultrasound, the release percentages from the loaded Fe-NDC-M and Fe-NDC-O at 37°C were found to be 2.3 and 4.9 %, respectively, after 10 min. These percentages increased significantly after applying 40-kHz ultrasound to reach 22.7 and 79.7 % for Fe-NDC-M and Fe-NDC-O, respectively. To confirm the ultrasound effect in triggering the release, the loaded Fe-NDC-M particles were exposed to another ultrasound frequency (20-kHz) at room temperature. After 10 min, the particles released 37.5% of the encapsulated model drug, compared to 1.7% without ultrasound.