Design and characterization of intravitreal bevacizumab-loaded PLGA nanoparticles: pharmacokinetic and biodistribution impact

Abstract

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.