Protective effect of water-soluble nervonic acid micro-powder coated with chitosan oligosaccharide and silk fibroin on hippocampal neuronal HT22 cells

Nervonic acid (NA) is an extremely long chain monounsaturated fatty acid that plays a crucial biological role in brain development and repair. However, its low solubility reduced bioavailability and limited its applications. In this study, spherical water-soluble nervonic acid composite micro-powder (NA-WM) was constructed by layer-by-layer self-assembly technology under electrostatic interaction and hydrogen bond, in which electronegative NA was used as the core material, and electropositive COS (Chitosan oligosaccharide) with neuroprotective properties and electronegative SF (Silk fibroin) with biocompatibility and anti-inflammatory synergism were used as the wall material. In the preparation process, the electronegative NA was first combined with electropositive COS by antisolvent method, and then the electropositive COS-NA complex was encapsulated with electronegative SF to form NA-WM. The optimal preparation conditions were screened and optimized via single-factor and BBD method. Under the optimum conditions, the average particle size of NA-WM was 420 ± 35 nm. The results of TGA (Thermogravimetric), SEM (Scanning electron microscopy), and FTIR (Fourier transform infrared spectroscopy) confirmed that NA-WM had good thermal stability and spherical-defined layer-to-layer structure. Additionally, at pH 1.5, the NA release rate of NA-WM was as high as 89.54 % within 2.5 h. Through measuring the levels of MDA (Malondialdehyde), CAT (Catalase), SOD (Superoxide dismutase), GSH-Px (Glutathione peroxidase), and LDH (Lactate dehydrogenase), as well as flow cytometry and SEM analysis, it was confirmed that NA-WM could protect Aβ1-42-induced HT22 by inhibiting oxidative stress and reducing mitochondrial membrane potential. This study provided data support for the development and application of NA.