Se nanoparticles-coated, PLGA-based spheres for biomedical applications: Cytotoxicity, genotoxicity, oxidative stress, biodistribution, and scintigraphic study

Conventional approaches to prevent and treat diseases, particularly liver disorders, often fall short, highlighting the urgent need for innovative strategies and materials in RNA therapeutics and genetic drug delivery. This study investigates the synthesis, characterization, and biological evaluation of poly (DL-lactide-co-glycolide) (PLGA) spherical particles as a novel drug delivery system for selenium nanoparticles (SeNp), presenting a promising (PLGA/SeNp) platform for enhancing the efficacy of genetic therapies aimed at liver diseases. We assessed the effects of PLGA/SeNp nanoparticles <i>in vitro</i> using human hepatoma cell lines (HepG2 cells), focusing on (i) cell viability, (ii) intracellular reactive oxygen species (ROS) generation, and (iii) genotoxic response. The findings indicated that PLGA/SeNp nanoparticles maintained cell viability, exhibited minimal ROS generation, and demonstrated low genotoxicity, underscoring their biocompatibility for therapeutic applications. Furthermore, this study explored the <i>in vivo</i> biodistribution and pharmacokinetics of PLGA and PLGA/SeNp particles through non-invasive dynamic imaging techniques. By radiolabeling with technetium-99m (Tc^99m), we conducted scintigraphic imaging to analyze biodistribution. Our <i>in vivo</i> results revealed significant differences in the biodistribution profiles of PLGA and PLGA/SeNp formulations at 24 h post-injection, with PLGA/SeNp showing enhanced hepatic, splenic, and pulmonary uptake compared to PLGA. These findings emphasize the unique pharmacokinetic properties of the PLGA/SeNp system, presenting a viable option for RNA-based therapeutics in liver disease management.