Varela-Fernández Rubén, García-Otero Xurxo, Cuartero-Martínez Andrea, Gómez-Lado Noemí, González-Barcia Miguel, Mondelo-García Cristina, Aguiar Pablo, Fernández-Ferreiro Anxo, Otero-Espinar Francisco
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, 15782, Spain.
Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, 15706, Spain.
Drug Deliv Transl Res. 2025 Jun 5. doi: 10.1007/s13346-025-01891-z.
Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF) for treating neovascular and oncological conditions, faces challenges in biodistribution and targeted delivery. Nanoparticle-based drug delivery systems have shown promise in enhancing the pharmacokinetic profiles of biologic drugs. This study aimed to develop and characterize bevacizumab-loaded PLGA nanoparticles to modify antibody's distribution and improve its therapeutic efficacy. Characterization studies, morphological examination, release profile determination, stability and physical properties were conducted. Biodistribution was studied in rats using PET/CT imaging. Optimized nanoparticles were spherical (around 300 nm) and surface charge (about - 20 mV). Encapsulation efficiency and drug loading varied from 75 to 95%. Stability studies demonstrated minimal changes in size and drug content over the studied period. In vitro release exhibited a biphasic pattern, with an initial burst followed by a sustained release phase. In vivo pharmacokinetics and distribution revealed altered antibody distribution by encapsulation into nanoparticles. Safety studies indicated no significant cytotoxicity or adverse effects. The developed bevacizumab nanoparticles demonstrated favorable physicochemical characteristics, stability, and release profiles. These findings warrant further investigation in disease-specific models to elucidate the clinical potential of this nanoparticle-based delivery system for bevacizumab, particularly in enhancing anti-angiogenic effects and overcoming barriers to effective delivery in target tissues.
贝伐单抗是一种靶向血管内皮生长因子（VEGF）用于治疗新生血管和肿瘤疾病的单克隆抗体，在生物分布和靶向递送方面面临挑战。基于纳米颗粒的药物递送系统在改善生物药物的药代动力学特征方面已显示出前景。本研究旨在开发和表征负载贝伐单抗的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒，以改变抗体的分布并提高其治疗效果。进行了表征研究、形态学检查、释放曲线测定、稳定性和物理性质研究。使用正电子发射断层扫描/计算机断层扫描（PET/CT）成像在大鼠中研究了生物分布。优化后的纳米颗粒呈球形（约300nm），表面电荷约为-20mV。包封率和载药量在75%至95%之间。稳定性研究表明，在所研究的时间段内，纳米颗粒的大小和药物含量变化极小。体外释放呈现双相模式，先是初始突释，随后是缓释阶段。体内药代动力学和分布研究表明，通过将抗体包封到纳米颗粒中，其分布发生了改变。安全性研究表明没有明显的细胞毒性或不良反应。所开发的负载贝伐单抗的纳米颗粒表现出良好的理化特性、稳定性和释放曲线。这些发现值得在疾病特异性模型中进一步研究，以阐明这种基于纳米颗粒的贝伐单抗递送系统的临床潜力，特别是在增强抗血管生成作用和克服靶组织中有效递送的障碍方面。
