A Self-Healing Metal–Organic Gel (MOG) Exhibiting pH-Responsive Release of a Chemotherapeutic Agent, Doxorubicin: Modulation of Release Kinetics by Partial Dehydration of Matrix

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 Cr 3+ -based metal− organic gel (MOG1) was synthesized from Cr(NO 3 ) 3 •9H 2 O 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.

Toxic metal–organic gels using a unique pyridine–pyrazole based ligand with Pb(ii), Cd(ii) and Hg(ii) salts: multi-stimuli responsiveness and toxic dye adsorption

“…After that MOG2 breaks down at 12.8% and MOG3 breaks at 23.7% strain. Pb gel transforms into sol at 62.5 % strain which is quite high enough indicating the strong nature of the gel material due to the formation of strong coordination bond with the metal ion 40 .Thixotropic results also showed the stronger nature of the Pb gel in comparison to the other gel materials (Figure 4d-f).…”

Hierarchical porous metal–organic gels and derived materials: from fundamentals to potential applications

“…131,213,214 The related class of MOGs can help overcome some of these limitations through their viscoelasticity that facilitates the shaping process, while maintaining most of the physicochemical properties of the parent MOFs. 156,215,216 The gas adsorption and separation performance of MOGs are commonly comparable with their parent MOFs; however, in some cases the MOG might even perform better. 131,[216][217][218] For instance, sol-gel synthesis routes have been established, which lead to a densification of the resulting pristine MOGs, increasing the volumetric gas adsorption.…”

Self-Templated Conversion of a Self-Healing Metallogel into an Active Carbon Quasiaerogel: Boosting Photocatalytic CO2 Reduction by Water

“…Typically, self-healing processes to restore the function and strength of materials after damage are either based on the presence of passive molecular functionalities that activate repair through stimuli-responsive reversible interactions, such as hydrogen bonding, metal coordination, molecular recognition, electrostatic interactions, molecular diffusion and entanglement, dynamic chemical bonds, and hydrophobic and π–π stacking association, or on the preservation of the healing agent in response to damage (in such scenario, the availability of the healing agents is locally depleted and hence iterative healing is generally not possible). − Self-healing in supramolecular gel or in particular metallogel has been studied via any of the abovementioned interactions. The metallogel materials are composed of metal ions and low-molecular-weight gelators, which contain a large amount of solvent molecules in their gel network structure. − Supramolecular self-healing metallogels (SHMGs) find a wide range of potential use from environmental remediation to luminescence applications. − Recently, Maji and co-workers reported a coordination polymer gel-based material with excellent photocatalytic activity for CO 2 reduction in the presence of sacrificial agents. − However, the use of SHMGs as a template for the preparation of photocatalysts to convert CO 2 gas into feedstock is not reported until now in the literature.…”