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 n-alkyl carboxylic acids (Me–(CH₂)_n–COOH; n = 1–3, 10–15) and various nonsteroidal anti-inflammatory drugs (NSAIDs), namely, indomethacin (IND), diclofenac (DIC), meclofenamic acid (MEC), tolfenamic acid (TOL), and flufenamic acid (FLU) (designated as salts 1–14, respectively) were synthesized as potential hydrogelators. Gelation studies revealed that mafenide n-alkyl carboxylates with n = 11–14, i.e., salts 5–8, and the indomethacin salt of mafenide, i.e., salt 10, were hydrogelators. The corresponding hydrogels, namely, 5­(HG)–8­(HG) and 10­(HG), were characterized by table-top and dynamic rheology and high-resolution transmission electron microscopy (HR-TEM). Single-crystal structures of the nongelator salts 1–3 and the gelator salt 10 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 10, the antibacterial response (zone inhibition assay) of salt 10, its components, and 10(HG), and the release of salt 10 in vitro 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.