Intravitreal Administration of Adalimumab-Loaded Poly(Lactic-co-Glycolic Acid) Nanoparticles: Effects on Biodistribution and Pharmacokinetics.

Adalimumab, a monoclonal antibody used for treating inflammatory diseases, including eye diseases, faces challenges in biodistribution and targeted delivery. Nanoparticle (NP)-based drug delivery systems have shown promise in enhancing the pharmacokinetic profiles of biologic drugs. This study aims to develop, and characterize intravitreal adalimumab-loaded poly(lactic-co-glycolic acid) (PLGA) NPs to improve antibody distribution and therapeutic efficacy. Characterization studies, morphological examination, and quantitative, stability, and physical properties are conducted. In vitro release kinetics are assessed using a dialysis membrane method. In vivo biodistribution is studied in rats after intravitreal administration by Positron Emission Tomography/Computed Tomography imaging. The optimized NPs were spherical (around 300 nm) with a surface charge of about -20 mV. Encapsulation efficiency and drug loading reach values close to 100%. Stability studies showed minimal changes in particle size and drug content. In vitro release showed a biphasic pattern with an initial burst release followed by sustained release. Safety studies indicated no significant cytotoxicity or adverse effects. The adalimumab-loaded PLGA NPs demonstrate favorable physicochemical characteristics, stability, and release profiles. In vivo distribution revealed a change in the antibody's distribution pattern after intravitreal administration via NPs encapsulation. These findings suggest the potential for enhanced therapeutic outcomes and warrant further investigation in disease-specific models to explore the clinical potential of this NP-based delivery system.