Studies of Encapsulation by Sorption, Characterization, and Release of Anti-Cancer Drug 6-Thioguanine from Aluminum Metal-Organic Framework Basolite A100
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Type of WorkText
ProgramMaster of Science
Metal-organic frameworks (MOFs) have already gained prominence in materials science research due to their high loading capacity and structural variability. Initial research showed the capabilities being used toward applications like gas sequestration, but contemporary investigations have shown a wider variety of uses, such as drug encapsulation and release. The MOF Basolite A100 (A100), with its relatively high biocompatibility, moderate pore size and plentiful commercial availability, was selected to further look in to the use of MOFs as a drug delivery platform. For a model drug, the anti-cancer compound 6-Thioguanine (6-TG) was chosen for its molecular size, novelty and use in therapeutic treatments compatible with MOF delivery. This thesis will show a method toward the encapsulation of 6-TG using dimethyl sulfoxide (DMSO) as solvent, and characterize the resultant complex A100-DMSO-6TG via X-ray diffraction (XRD), fluorescence spectroscopy and differential scanning calorimetry (DSC). In addition, the release kinetics of the 6-TG from two different forms of the complex in a phosphate buffer saline (PBS) were studied via high performance liquid chromatography (HPLC). It was observed that 6-TG resides in two locations in the cavity of A100 and forms bonds both directly between itself and the A100 as well as through the DMSO molecule to the A100. This results in an initial quick release of the surface bound 6-TG and the secondary release of the 6-TG from the cavity, a process slowed by pelletizing. Chemical kinetics of delayed release suggests a future potential therapeutic use based on initial cytotoxicity followed by growth inhibition, with much room for future studies along this axis.