This study describes the development of β-cyclodextrin (β-CD) inclusion complexes of curcumin (CUR) and a synthetic curcuminoid analogue (CN56), which were incorporated into poly(vinyl alcohol)/κ-carrageenan hydrogel films to create a multifunctional system capable of sustained drug release and effective antimicrobial action. Carrageenan was extracted from Gigartina skottsbergii, and hydrogels were prepared using a freeze–thaw crosslinking method. The inclusion complexes were formed at a 1:6 molar ratio, achieving loading efficiencies of 75.62% for CUR and 79.00% for CN56. FTIR confirmed molecular interactions between the complexes and the polymeric matrix, accompanied by reduced crystallinity and increased amorphous character. Thermogravimetric analysis revealed enhanced thermal stability, with degradation onset temperatures above 239 °C, while DSC analysis indicated irreversible amorphization after the first heating cycle. SEM analysis showed improved surface uniformity in complex-loaded films compared with those containing free compounds. Swelling experiments demonstrated significantly greater fluid uptake in complex-loaded hydrogels, particularly for CN56 (1080% after 45 min). Controlled release studies revealed sustained drug release profiles, with 76.49% of CUR and 56.02% of CN56 released over 36 h, following Fickian diffusion mechanisms. In vitro antimicrobial assays confirmed marked activity of CUR and CN56 against Gardnerella vaginalis, a key pathogen associated with bacterial vaginosis. Biocompatibility tests, including hemolysis and MTT reduction assays, indicated low cytotoxicity and satisfactory hemocompatibility. Rheological analysis further demonstrated increased viscosity and potential mucoadhesive behavior. Collectively, these findings highlight the potential of carrageenan-based PVA hydrogels as innovative pharmaceutical platforms for the prevention and treatment of recurrent bacterial vaginosis, offering a promising alternative to conventional therapies.

Antimicrobial resistance is a critical global concern. This study explored the lipid extract (LE) of Ulva ohnoi regarding its chemical composition, antibacterial activity, and cytotoxicity against multidrug-resistant (MDR) microorganisms. The LE was characterized by GC–MS, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Antibacterial efficacy was determined by Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against MDR isolates: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative Staphylococci (CoNS). Cytotoxicity was evaluated in murine fibroblast (L929) and bovine renal fibroblast (MDBK) cells using MTT, Neutral Red (NR), Lactate Dehydrogenase (LDH), and hemolytic activity (HA) assays. Lipid characterization revealed palmitic acid (63.62%) and oleic acid (21.01%) as major components. TGA indicated 88% mass loss, and DSC showed no amorphous/crystalline domains. LE showed favorable MIC values against S. aureus and CoNS (1.33 mg/mL) and against A. baumannii and E. coli (2 mg/mL), indicating moderate antibacterial activity typical of an unfractionated crude extract. MBC results indicated bacteriostatic activity (1–8 mg/mL). The extract was cytotoxic to L929 and MDBK cells at concentrations close to its MIC (IC₅₀ 0.25–1.95 mg/mL) but well tolerated by blood cells (HA IC₅₀ 4.705 mg/mL). U. ohnoi LE extends, rather than establishes, the previously reported antibacterial potential of Ulva lipids through comprehensive chemical characterization and MDR-isolate evaluation. However, low selectivity indices (SI < 10) indicate that the LE does not yet present an adequate therapeutic window, reinforcing the need for bioassay-guided purification. Nevertheless, it is a starting point for developing new antibacterial agents. Graphical Abstract