(190u) Encapsulation of 6-Thioguanine on Al-MOF Basolite A100 and Its Controlled Delivery

6-Thioguanine (6-TG) is a major
FDA-approved anti-leukemia drug, which however
features the limited bioavailability and short plasma half-life due to quick metabolization. For an efficient prolonged local delivery,
6-TG needs to be encapsulated on a suitable non-toxic insoluble carrier. Metal-Organic
Frameworks (MOFs) are promising nanomaterials for
encapsulation of small-molecule drugs by sorption and controlled drug delivery.
We report studies of encapsulation of 6-TG by sorption on non-toxic, chemically
stable, water-insoluble microporous aluminium MOF (Al-MOF)
Basolite A100. Sorption of 6-TG on Basolite A100 from non-toxic, the FDA-approved solvent dimethylsulfoxide (DMSO) yields the ternary adsorption
complex A100/6-TG/DMSO or the stoichiometric binary complex A100/DMSO. We also
report the spectroscopic, thermal and structural characterization of the adsorption
complexes, the in-vitro kinetics of time-controlled delivery of 6-TG from the
complexes, and cytotoxicity studies. To learn about chemical bonding of drug
molecules in the adsorption complexes, we utilized, for the first time, the
solid-state front face (FF) 3-dimensional fluorescence emission spectroscopy at
25 °C. The fluorescence spectra of Basolite A100 show
the distinct bands in the near-UV and visible range due to “monomers” of benzenedicarboxylic acid (BDC) linker and ligand-to-ligand
charge transfer (LLCT). Upon encapsulation of 6-TG and DMSO, the fluorescence
spectra undergo selective quenching of fluorescence bands, due to specific binding
of co-adsorbate molecules of 6-TG and DMSO. Based on
differential scanning calorimetry (DSC) data, DMSO is
strongly bound to Basolite A100 in the complex.
Nevertheless, DMSO is promptly released (<30 min.) from the adsorption
complex to simulated bodily fluid (SBF) at 37 ºC and pH 7.4 as determined by
the reverse-phase HPLC. On the other hand, the differential release of 6-TG from
the ternary adsorption complex proceeds on a >24 h. time scale. While pure
6-TG undergoes hydrolysis with the decrease of concentration, the 6-TG in the ternary
complex with Basolite A100 features kinetic “profile”
of pre-programmed drug delivery with the increase in concentration. Finally, studies
with acute
myeloid leukemia (AML) MV4-11 cell culture indicate the substantial cytotoxicity
of the ternary adsorption complex of Basolite A100 with 6-TG and DMSO. Non-toxic water-stable MOF Basolite A100 is a promising drug-encapsulation platform for
the time-programmed delivery of small-molecule drugs.