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

IF 4.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-09-04 DOI:10.1016/j.ejpb.2025.114860

Ahmad Mavali Zadeh , Emanuela Gatto , Raffaella Lettieri , Honey Bokharaie , Alice Caravella , Cadia D’Ottavi , Elisabetta di Bartolomeo , Fabio Domenici , Setareh Sima , Alexandra Correia , Khushbu Rauniyar , Anna Klose , Zahra Gounani , Timo Laaksonen , Jaana Künnapuu , Michael Jeltsch

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引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

用于血管内皮生长因子- c持续递送的生物质衍生木质素纳米颗粒。

血管内皮生长因子C （VEGFC）是一种很有前景的生物药物，临床前研究表明其治疗心肌梗死、神经退行性疾病和淋巴水肿的潜力，这些疾病目前缺乏根治性治疗。虽然腺病毒VEGFC基因治疗已进展到II期研究，但其临床疗效受到快速免疫失活的限制。本研究探索木质素纳米颗粒（LNPs）作为VEGFC的替代递送系统。采用有机溶剂法从葡萄嫩枝衍生的木材生物质中提取木质素，用于合成LNPs。利用动态光散射和显微技术对所制得的粒子进行了全面表征，其Z-Average为143.6 nm， PDI为0.126，zeta电位为-41 ± 8 mV，并评价了其结构和形态特征。评估VEGFC加载和释放概况，显示有效加载和控制释放能力。采用3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四唑（MTT）测定法评估血浆稳定性和细胞活力，以评估生物相容性和治疗潜力。我们的数据表明，VEGFC本身是相对稳定的，这表明LNPs的关键优势在于它们调节释放谱的能力，而不是保护蛋白质免于降解/失活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Pharmaceutics and Biopharmaceutics 医学-药学

CiteScore

8.80

自引率

4.10%

发文量

211

审稿时长

36 days

期刊介绍： The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.