Biomass-derived Lignin Nanoparticles for the Sustained Delivery of Vascular Endothelial Growth Factor-C

Abstract

Vascular Endothelial Growth Factor C (VEGFC) is a promising biological drug, as preclinical studies have shown its potential in treating a variety of conditions, including myocardial infarction and neurodegenerative diseases. For lymphedema, a disease that currently can only be treated symptomatically, adenoviral VEGFC gene therapy has been evaluated up to phase II studies. However, the AdVEGFC is rapidly inactivated by the immune system, and alternative delivery methods might yield better results. Thus, we wanted to investigate the synthesis, characterization, and stability of lignin nanoparticles (LNPs) as carriers for VEGFC. As biomass-derived lignin nanoparticles provide a sustainable, cost-effective, and tunable platform for drug delivery, with the potential to enhance drug stability and release, lignin was extracted from wood biomass derived from grape shoots using the organosolv method and subsequently synthesized into nanoparticles. The resulting lignin nanoparticles (LNPs), with an average size of 142{+/-}62 nm and a zeta potential of -40{+/-}8 mV, were characterized through comprehensive techniques, including spectroscopy and microscopy, to gain insights into their structural and morphological properties. Furthermore, the loading and release efficiency of VEGFC onto LNPs were evaluated, demonstrating effective loading and controlled release. Stability tests in plasma and cell proliferation/viability assessments using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay were conducted to assess biocompatibility and therapeutic potential. Our data shows that VEGFC is a relatively stable protein and that the primary advantage of nanoparticle-based delivery would be to delay release as opposed to protect VEGFC from degradation/inactivation. Graphical AbstractFlow chart of the generation and analysis of biomass-derived VEGFC-loaded lignin nanoparticles. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/649697v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1476841org.highwire.dtl.DTLVardef@10d861corg.highwire.dtl.DTLVardef@dfa209org.highwire.dtl.DTLVardef@72c81_HPS_FORMAT_FIGEXP M_FIG C_FIG