Natural Molecule-Derived Nanogels from Hematoxylin and l-lysine for Biomedical Use with Antimicrobial Properties

Hematoxylin (HT) is a natural staining dye used in histopathology, often combined with Eosin for H&E staining. A poly(hematoxylin-co-l-lysine) (p(HT-co-l)) nanonetwork was synthesized through a one-step Mannich condensation reaction using formaldehyde as a linking agent. The resulting p(HT-co-l) nanogels had an average size of about 200 nm and exhibited a smooth surface and desirable functional groups such as -OH, -NH₂, and -COOH, as recognized by FT-IR analysis. The isoelectric point (IEP) of the p(HT-co-l) nanogel was determined as pH 7.9, close to physiological environments, despite HT being acidic IEP at pH 1.7 and l-lysine being basic IPE at pH 8.7. The time-dependent swelling studies of p(HT-co-l) nanogels were carried out using dynamic light scattering (DLS) in different salt solutions, e.g., MgCl₂, KNO₃, KCl, PBS, and DI water environments revealed that nanogels have high swelling ability depending on the medium, e.g., >10-fold in a saline solution compared to distilled water within 1.5 h. Hydrolytic degradation studies in PBS demonstrated a linear release profile up to 125 h at 37.5 °C. The p(HT-co-l) nanogels also demonstrated significant antimicrobial and antifungal activities against <i>E. coli</i> (ATCC 8739), <i>S. aureus</i> (ATCC 6538), and <i>C. albicans</i> (ATCC 10231). Furthermore, biocompatibility tests indicated that p(HT-co-l) nanogels are more biocompatible than HT alone, as tested with human Nuli-1 bronchial epithelial cells.