Alginate hydrogels as carriers of coumarin derivatives and a phosphonate analog: characterization by Raman and FT-IR and biocompatibility evaluation.

Abstract

Polysaccharide-based hydrogels are promising materials for wound healing, drug delivery, and tissue engineering due to their biocompatibility. However, incorporating hydrophobic aromatic compounds into hydrated matrices remains challenging. In this study, calcium-crosslinked sodium alginate hydrogels were loaded with coumarin (Cn), two substituted coumarin derivatives (Z1 and Z3), and a related allylic phosphonate analog (Z2) to obtain formulations with potential relevance for biomedical material development. Cytotoxicity testing showed that all compounds exhibited IC50 values above 100 μM, indicating low in vitro cytotoxicity toward HaCaT cells (IC50 ˃100 μM). The active substances (ASs) were successfully entrapped within alginate hydrogels without structural degradation, as confirmed by Raman and ATR-FTIR spectroscopy. Spectroscopic analysis suggested possible polymer-compound interactions. Release studies demonstrated that diffusion was likely influenced by matrix-compound interactions rather than compound solubility alone. The resulting hydrogels were highly hemocompatible, causing less than 0.1% hemolysis, and displayed composition-dependent functional responses. In the ABTS assay, Z1 showed the strongest radical-scavenging activity at 0.48 mg/mL. Preliminary antimicrobial testing indicated activity against Candida albicans; however, the contribution of DMSO as a solubilizing agent cannot be ruled out. Overall, the developed hydrogels provide a safe matrix primarily with physicochemical functionality and only preliminary biological indications, rather than demonstrated therapeutic efficacy.