Eutectogels as Delivery Media for Therapeutic Metal Complexes: What Are the Benefits?

Drugs and drug candidate compounds commonly suffer from poor solubility and permeability. One promising strategy to mediate these drawbacks is use of novel solvents, such as deep eutectic compositions. The present research aims to determine the applicability of this approach for therapeutic metal complexes on the example of [Cu(Fur)₂(Phen)] (Fur = furoate-anion, Phen = 1,10-phenantroline) and [Cu(Fur)₂(Neoc)(H₂O)] (Fur = furoate-anion, Neoc = 2,9-dimetyl-1,10-phenanthroline) with molar weight of appx. 500 Da. Interaction of the metal complexes with the deep eutectic solvent (DES) reline was studied using electron paramagnetic resonance (EPR). Minimal inhibitory concentrations of the complexes dissolved in DES and dimethyl sulfoxide (DMSO) were determined and found to be equivalent in both solvents. That is, use of reline as a solvent did not alter the functional properties of the metal complexes. Changes in the transdermal permeation of the complexes in DMSO and DES were assessed using a Franz diffusion cell. It was discovered that depending on the structure of the complex, the permeability might either increase (from 15 to 30%) or decrease (from 13 to 8%) with changes in the solvent, and this can be used to develop dosing strategies. Therapeutic eutectogels were successfully produced by impregnating SiO₂ nanoparticles with the metal complex solution in DES, facilitating convenient topical application.