Electrostatic Loading and Photoredox-Accelerated Release of Antibiotics from Oligoviologen-Crosslinked Hydrogels...

Hydrogel drug delivery is the subject of an ever-expanding industry where delivery occurs by numerous methods, many of them passive in nature. On-command, stimuli-driven release, particularly using light to initiate spatiotemporal, controlled release of cargo is a more attractive approach than passive release methods. Here, we report a novel method for electrostatically loading negatively charged dye and antibiotic cargo in biocompatible, oligoviologen-crosslinked hydrogels equipped with an integrated Aza-boron-dipyrromethene (Aza-BODIPY) photocatalyst. Following loading, the release of the electrostatically bound cargos can be accelerated upon irradiation with red light (660 nm) through a photoinduced electron transfer (PET) process that reduced the oligoviologen subunits. A free radical polymerization method was used to fabricate the hydrogels with a hydroxyethyl acrylate backbone, co-crosslinked by a viologen hexamer (6V-St•12Cl) and Aza-BODIPY derivative. Irradiation of the Aza-BODIPY photocatalyst led to a reduction of the viologen subunits to their monoradical cation oxidation state via PET. The photocatalyst was regenerated in situ in a triethanolamine (TEOA) solution, which served as a sacrificial reductant. Negatively charged dye (i.e., methyl orange, MO) was electrostatically loaded into the hydrogel through counteranion metathesis, followed by irradiation with red light to release the dye as the subunits of the viologen crosslinker lost positive charges (i.e., V²⁺ to V^●+). Controlled release of the dye was tracked by UV/Vis absorption spectroscopy, yielding up to 74% of cargo released in 75 h. Negatively charged antibiotic cargo (i.e., nalidixic acid) was then electrostatically loaded into and released from hydrogels by the same method. Controlled release of the drug was tracked by agar diffusion and liquid broth microdilution antibacterial susceptibility assays, where bacterial growth inhibition was recorded, confirming the same release trends observed for the dye cargo.