Abstract:
Use of soft and porous metal−organic gels (MOGs),
formed by metal−ligand coordination, has generated immense research
interest in fields like conductance, catalysis, chemical sensing, and dye
adsorption, but there are only few reports on their use in drug delivery,
particularly cancer drug delivery. Consequently, a Cr3+-based metal−
organic gel (MOG1) was synthesized from Cr(NO3)3·9H2O and 2,2′-
bipyridine-4,4′-dicarboxylic acid (BPDA) in DMF, using a solvothermal
route. The gel exhibited strong resilience when subjected to a dynamic
frequency sweep from 1−100 rad/sec at a constant strain of 0.1% and
minimal loss of storage modulus when subjected to repeated cycles of 0.1
and 100% strain for 60 s, and it exhibited self-healing characteristics. The
doxorubicin (DOX)-loaded gels were developed to assess the drug release
profiles at physiological (7.4) and intratumoral (6.4) pH and found to be
pH-dependent. A sustained zero-order release of 54% drug was obtained
after 48 h at pH 7.4 and, a faster release, with 87.4% of the drug being released in 12 h following pseudo-Fickian diffusion at pH
6.4. The most unique feature of the gel, not reported earlier, was the transformation of the drug release kinetics from zero order
to exponential decay upon dehydration to 80% of its original weight. The drug release slowed down further when the gel was
dehydrated to 50% of its original weight. The cell viability assay showed no significant toxicity of MOG1 to mdck (kidney
epithelial) cell lines, and more than 75% cells were viable, even after 72 h, with concentrations up to 100 μg/mL, whereas the
DOX-loaded MOG1 demonstrated dose-dependent toxicity to cancer cell lines (A549) in the concentration range investigated
(0.1−5 μg/mL equivalent DOX). Fluorescence microscopy studies revealed efficient internalization of DOX released from
MOG1 into cancer cells. The gel may be employed as an injectable depot for quick and selective delivery of a chemotherapeutic
agent to tumoral sites.
