Supramolecular Hydrogels Developed from Mafenide and Indomethacin as a Plausible Multidrug Self-Delivery System as Antibacterial and Anti-inflammatory Topical Gels

Following a structural rationale, a series of simple organic salts derived from mafenide (a drug for treating burn wounds) and <i>n</i>-alkyl carboxylic acids (Me–(CH₂)_n–COOH; <i>n</i> = 1–3, 10–15) and various nonsteroidal anti-inflammatory drugs (NSAIDs), namely, indomethacin (<b>IND)</b>, diclofenac (<b>DIC)</b>, meclofenamic acid (<b>MEC</b>), tolfenamic acid (<b>TOL</b>), and flufenamic acid (<b>FLU</b>) (designated as salts <b>1–14</b>, respectively) were synthesized as potential hydrogelators. Gelation studies revealed that mafenide <i>n</i>-alkyl carboxylates with <i>n</i> = 11–14, i.e., salts <b>5–8</b>, and the indomethacin salt of mafenide, i.e., salt <b>10</b>, were hydrogelators. The corresponding hydrogels, namely, <b>5­(HG)</b>–<b>8­(HG)</b> and <b>10­(HG)</b>, were characterized by table-top and dynamic rheology and high-resolution transmission electron microscopy (HR-TEM). Single-crystal structures of the nongelator salts <b>1</b>–<b>3</b> and the gelator salt <b>10</b> were determined by X-ray diffraction. The results obtained from various studies, which included the solubility, biostability, biocompatibility (MTT assay), and anti-inflammatory (PGE₂ assay) response of salt <b>10</b>, the antibacterial response (zone inhibition assay) of salt <b>10</b>, its components, and <b>10</b>(<b>HG</b>), and the release of salt <b>10</b> <i>in vitro</i> from the corresponding hydrogel bed to the bulk solvent at 37 °C in 24 h, suggested their plausible use in developing multidrug-derived topical hydrogels for self-delivery applications.