AChE Inhibition Capability of Nanogels Derived from Natural Molecules: Tannic Acid and Lysine for Alzheimer's Disease

Background/Objectives: Tannic acid (TA), a known natural polyphenolic acid with many bioactivities including antioxidants, antibacterial, and antiviral, can be combined with a natural essential amino acid L-lysine (LYS) in nanogel formulations to produce p(TA-co-LYS) (p(TA-co-LYS)) nanogels. Methods: A 1:1 mole ratio of TA:LYS was used to prepare corresponding spherical nanogels employing formaldehyde as a linker via the Mannich reaction. Results: The attained p(TA-co-LYS) particles were in 283 +/- 57 nm size ranges (via SEM analysis) and possessed smooth surfaces. The zeta potential measurements of p(TA-co-LYS) nanogels suspension at different solution pHs revealed the isoelectric point (IEP) of pH 4.9, suggesting that the particles are negatively charged at the physiological pH range (e.g., at 7.4). In addition to the antioxidant efficacy of nanogels confirmed by three different tests, p(TA-co-LYS) particles showed significant Fe(II) ion chelating capacity at 350 mu g/mL concentrations compared to bare TA, which is 21%, whereas the LYS molecule had a chelating capacity of 100% at the same concentrations. Moreover, it was found that p(TA-co-LYS) nanogels inhibited the Acetylcholinesterase enzyme (AChE) at a concentration-dependent profile, e.g., at 333 mu g/mL concentration of p(TA-co-LYS), 57.2% of the enzyme AChE activity was inhibited. Furthermore, the minimum inhibition concentrations of p(TA-co-LYS) nanogels of Gram-negative Escherichia coli (ATCC 8739) and Gram-positive Staphylococcus aureus (ATCC 6538) were determined as 12.5 mg/mL. Conclusions: As cytotoxicity studies of p(TA-co-LYS) nanogels on L929 fibroblast cells also ascertained that these particles can be safely used in many biomedical applications, including antioxidant materials, drug delivery devices, and enzyme inhibitors.