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 -alkyl carboxylic acids (Me-(CH)-COOH; = 1-3, 10-15) and various nonsteroidal anti-inflammatory drugs (NSAIDs), namely, indomethacin (, diclofenac (, meclofenamic acid (), tolfenamic acid (), and flufenamic acid () (designated as salts , respectively) were synthesized as potential hydrogelators. Gelation studies revealed that mafenide -alkyl carboxylates with = 11-14, i.e., salts , and the indomethacin salt of mafenide, i.e., salt , were hydrogelators. The corresponding hydrogels, namely, - and , were characterized by table-top and dynamic rheology and high-resolution transmission electron microscopy (HR-TEM). Single-crystal structures of the nongelator salts - and the gelator salt were determined by X-ray diffraction. The results obtained from various studies, which included the solubility, biostability, biocompatibility (MTT assay), and anti-inflammatory (PGE assay) response of salt , the antibacterial response (zone inhibition assay) of salt , its components, and (), and the release of salt 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.