Varela Fernández, RubénGarcía Otero, XurxoCuartero Martínez, AndreaGómez Lado, NoemíGonzález Barcia, MiguelMondelo García, CristinaAguiar Fernández, PabloFernández Ferreiro, AnxoOtero Espinar, Francisco Javier2025-07-242025-07-242025-06-05Varela-Fernández, R., García-Otero, X., Cuartero-Martínez, A. et al. Design and characterization of intravitreal bevacizumab-loaded PLGA nanoparticles: pharmacokinetic and biodistribution impact. Drug Deliv. and Transl. Res. (2025). https://doi.org/10.1007/s13346-025-01891-zhttps://hdl.handle.net/10347/42584Bevacizumab, 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.eng© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/BevacizumabPLGANanoparticlesControlled releaseBiodistributionPharmacokineticsjournal article10.1007/s13346-025-01891-z2190-3948open access