Chronic wounds, affecting over 10.5 million U.S. Medicare beneficiaries and exacerbated by diabetes, represent a critical healthcare challenge due to multifactorial pathophysiology, antimicrobial resistance, and inadequate therapeutic delivery. To address these limitations, we developed a novel beeswax-encapsulated emulsified formulation (F4) combining delafloxacin (DLX), lidocaine (LIDO), and sodium hyaluronate (SHA). F4 demonstrated high encapsulation efficiency (87.6–91.3%), optimal nanoparticle characteristics (115.68 nm, PDI 0.26, zeta potential −31.70 mV), and pH-responsive sustained release (94–100% cumulative release at 24 h, pH 7.4). Kinetic modeling confirmed a diffusion-controlled release mechanism (Korsmeyer–Peppas R² > 0.989), and comprehensive forced degradation studies coupled with in silico toxicological profiling (following ICH M7 guidelines) confirmed the formulation's stability and low impurity risk. Critically, F4 exhibited significantly enhanced antibacterial activity versus free DLX: larger inhibition zones against all tested pathogens (Gram-positive: S. aureus, B. subtilis; Gram-negative: E. coli, P. aeruginosa), 4-fold lower MICs against S. aureus (0.031 vs. 0.125 µg mL⁻¹) and E. coli (0.031 vs. 0.125 µg mL⁻¹), and potent bactericidal effects (MBC/MIC ≤ 2). F4 also disrupted biofilms at sub-MIC levels (1/16–1/64 MIC), comparable to ciprofloxacin, and achieved complete bactericidal killing of planktonic S. aureus within 12 h at 4× MIC. Furthermore, time-kill kinetics demonstrated a concentration-dependent bactericidal effect. Cytotoxicity assays confirmed enhanced biocompatibility (CC₅₀: 872.40 µg mL⁻¹), preserving >80% fibroblast viability at therapeutic doses. This multimodal platform concurrently addresses infection control (including biofilm resistance), analgesia, tissue regeneration, and controlled delivery, offering a transformative strategy for chronic wound management.

COVID-19 is still widespread worldwide and up to now there is no established antiviral able to control the disease. Main protease is responsible for the viral replication and transcription; thus, its inhibition is a promising route to control virus proliferation. The present study aims to examine detail interactions between main protease and recently reported ninety-seven inhibitors with available X-ray crystallography to define factors enhance inhibition activity; thirty-two of most potent inhibitors were examined to identify sites and types of interaction. The study showed formation of covalent bond, H-bond and hydrophobic interaction with key residues in the active side. Covalent bond is observed in seventeen complexes, all of them by attack of the 145Cys thiol group on Michael acceptor, aldehyde or its hydrate, α-ketoamide, double bond or acetamide methyl group; the latter type requires H-bonding between acetamide carbonyl oxygen and at least one of 143Gly, 144Ser or 145Cys. Potent inhibitors, disulfiram and ebselen docked in the same binding site. Accordingly, factors identify inhibition include forming covalent bond and existing terminal hydrophobic groups and amidic or peptidomimetic structure. Binding affinity was found correlated with topological diameter up to 24 bond, molecular size, branching, polar surface area up to 199 Ų and hydrophilicity.