6-Thioguanine (6-TG) is an FDA-approved antimetabolite leukemia drug, which however has short plasma half-life (~20 min.) and low bioavailability (~30%). For the prolonged delivery, 6-TG should be encapsulated on the suitable non-toxic insoluble carrier. Metal-Organic Frameworks, MOFs are promising for encapsulation of small-molecule drugs by sorption and controlled delivery. We report recent studies of encapsulation of 6-TG by sorption on non-toxic, stable, water-insoluble aluminum MOF (Al-MOF) Basolite A100. Sorption of 6-TG on Basolite A100 from the FDA-approved solvent dimethyl sulfoxide (DMSO) results in the ternary sorption complex A100/DMSO/6-TG or the stoichiometric binary complex A100/DMSO. We describe the spectroscopic, thermal, and structural characterization of sorption complexes, kinetics of <i>in-vitro</i> delivery of 6-TG, and cytotoxicity. To study chemical bonding of drug molecules in the complexes, we utilized solid-state front face (FF) 3-dimensional fluorescence emission spectroscopy at 25 °C. The spectra of Basolite A100 show the distinct emission bands in the near-UV and visible range due to monomers of benzenedicarboxylate (BDC) linker and ligand-to-ligand charge transfer (LLCT). After encapsulation of 6-TG and DMSO, the fluorescence spectra undergo selective quenching due to specific binding of co-adsorbates 6-TG and DMSO. From the data by differential scanning calorimetry (DSC), DMSO is strongly bound to linkers in Basolite A100, but is promptly released (&lt;30 min.) from the complex to simulated bodily fluid (SBF) at 37 °C and pH 7.4. The release of 6-TG from the ternary complex proceeds on a &gt;24 h. time scale. While pure 6-TG undergoes hydrolysis, the 6-TG in the ternary complex features the favorable kinetic profile of pre-programmed delivery with an increase of concentration. The cytotoxicity tests with acute myeloid leukemia (AML) MV4-11 cells indicate the substantial toxicity of the ternary complex. The water-stable and non-toxic Al-MOF Basolite A100 is promising for encapsulation and time-programmed delivery of small-molecule drugs.

Encapsulation and controlled release of antimetabolite drug 6-thioguanine from aluminum metal-organic framework

2019 Spring National Meeting

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