Biodistribution and Toxicological Impact Assessment of Cerium Dioxide Nanoparticles in Murine Models: A Systematic Review of In Vivo and Ex Vivo Studies.

Background/Objectives: This review summarizes and analyzes current data on the toxicological effects of cerium dioxide nanoparticles (nanoceria) on various anatomical and functional systems in healthy murine models, as reported in both in vivo and ex vivo experimental settings. Methods: This systematic review was conducted and reported in accordance with the PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42024503240). A systematic literature search was conducted using the PubMed and ScienceDirect databases for the period 2019-2025, with the inclusion of earlier publications having significant scientific relevance. The final search update was conducted in July 2025 to ensure inclusion of the most recent studies. Results and Conclusions: Only in vivo and ex vivo studies in healthy murine models were included. Risk of bias was evaluated using the OHAT tool for animal studies, and data were synthesized narratively due to heterogeneity among studies. A total of 29 studies met the inclusion criteria. The pharmacokinetic properties of nanoceria were considered, encompassing biodistribution, elimination pathways (including oral, intravenous, intraperitoneal, inhalation, intratracheal, and instillation routes), and the influence of physicochemical characteristics on bioavailability and toxicity. The toxicological impact (TI) was assessed across major organ systems-respiratory, digestive, urinary, visual, reproductive, nervous, cardiovascular, immune, hematopoietic, endocrine, musculoskeletal, and skin. The liver, spleen, lungs, and kidneys were identified as primary accumulation sites, with clearance dependent on particle size and coating. The TI spectrum ranged from the absence of morphological changes to inflammation, fibrosis, or organ dysfunction, depending on dose, exposure route, and physicochemical parameters. The main limitations include variability of nanoparticle formulations and incomplete toxicity reporting. In general, CeO2 nanoparticles with sizes of 2-10 nm and doses ≤ 5 mg/kg showed no signs of systemic toxicity in short-term studies on healthy mice, provided that optimal coating and dosing intervals were used.