Phenolation of Lignin for the Formation of Stable and Biofunctional Nanoparticles: Nanoprecipitation vs Solvent Exchange

Azma Fakhar1*, Joon Weon Choi1,2

(1Graduate School of International Agricultural Technology, Seoul National University,

2Institutes of Green-Bio Science and Technology, Seoul National University)

Abstract: Lignin is a renewable biopolymer with promising biomedical potential due to its antioxidant and antimicrobial properties, but its structural heterogeneity and limited reactivity hinder broader applications. In this study, Kraft lignin and Milled wood lignin were phenolated to enhance their reactivity and nanoparticle-forming ability, followed by a comparison of nanoparticle fabrication via nanoprecipitation and solvent exchange. Phenolation increased phenolic hydroxyl content to 3.65 mmol g⁻¹ for Kraft lignin and 2.10 mmol g⁻¹ for Milled wood lignin, as confirmed by ³¹P NMR and 2D-HSQC analyses. These structural modifications improved lignin solubility and reactivity. Nanoprecipitation produced stable, monodisperse lignin nanoparticles (90–160 nm, PDI < 0.1, zeta potential −26 to −45 mV), while solvent exchange resulted in larger, less stable particles (550–800 nm). Phenolated lignin nanoparticles prepared by nanoprecipitation showed superior antioxidant activity. Overall, phenolation combined with nanoprecipitation enables the production of stable, functional lignin nanoparticles with strong potential for biomedical applications such as drug delivery and tissue engineering.

Keywords: Lignin nanoparticles, Phenolation, Nanoprecipitation, Biomedical application, Antioxidant and antimicrobial activity