Sima, S. | bioRxiv Science

bioRxiv2025

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, 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

pharmacology and toxicology↗

bioRxiv2023

Same principle, but different computations in representing time and space

Time and space are two intertwined contexts that frame our cognition of the world and have shared mechanisms. A well-known theory on this case is A Theory of Magnitude (ATOM) which states that the perception of these two domains shares common mechanisms. However, evidence regarding shared computations of time and space is intermixed. To investigate this issue, we asked human subjects to reproduce time and distance intervals with saccadic eye movements in similarly designed tasks. We applied an observer model to both modalities and found underlying differences the processing of time and space. While time and space computations are both probabilistic, adding prior to space perception minimally improved model performance, as opposed to time perception which was consistently better explained by Bayesian computations. We also showed that while both measurement and motor variability were smaller in distance than time reproduction, only the motor variability was correlated between them, as both tasks used saccadic eye movements for response. Our results suggest that time and space perception abide by the same algorithm but have different computational properties.

neuroscience↗