Biomass-derived lignin nanoparticles for the sustained delivery of vascular endothelial growth factor-C.

Vascular Endothelial Growth Factor C (VEGFC) is a promising biological drug, with preclinical studies indicating its potential for treating myocardial infarction, neurodegenerative diseases, and lymphedema, a condition that currently lacks curative treatment. While adenoviral VEGFC gene therapy has progressed to phase II studies, its clinical efficacy is limited by rapid immune inactivation. This study explores lignin nanoparticles (LNPs) as an alternative VEGFC delivery system. Lignin was extracted from grape shoot-derived wood biomass via the organosolv method and used to synthesize LNPs. The resulting particles, with a Z-Average of 143.6 nm, a PDI of 0.126 and a zeta potential of -41 ± 8 mV, were thoroughly characterized using dynamic light scattering and microscopic techniques to evaluate their structural and morphological features. VEGFC loading and release profiles were assessed, showing efficient loading and controlled release capabilities. Stability in plasma and cell viability were evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay to assess biocompatibility and therapeutic potential. Our data indicate that VEGFC is relatively stable on its own, suggesting that the key advantage of LNPs lies in their ability to modulate the release profile rather than protect the protein from degradation/inactivation.