Iron Oxide Nanoparticles Integrated in 3D-Printed Dosage Forms for Advanced Iron Supplementation

Abstract

Iron deficiency remains a major global health burden, and conventional oral supplements based on Fe salts are often limited by poor bioavailability and gastrointestinal intolerance. Here, we report an innovative strategy that integrates iron oxide nanoparticles (Fe₃O₄ NPs) into three-dimensional (3D) printed tablets (printlets) as advanced oral dosage forms for iron supplementation. Bare and citrate-coated Fe₃O₄ NPs were synthesized, dispersed in glycerol, and incorporated into poly(vinyl alcohol) filaments via hot-melt extrusion, which enabled fabrication of uniform cylindrical tablets through fused deposition modeling (FDM). Structural and spectroscopic analyses confirmed successful incorporation and homogeneous distribution of NPs within the polymeric matrix, while mechanical testing demonstrated that stable glycerol-based dispersions yielded filaments with superior strength and printability compared to powder-based mixtures. Dissolution studies under simulated gastric and intestinal conditions revealed rapid and complete iron release for both formulations at pH 1.0, whereas citrate-functionalized NPs significantly enhanced iron release at pH 6.8, correlating with improved colloidal stabilization of the supernanostructures generated during dissolution. Zebrafish embryo assays further indicated low acute toxicity for both nanoparticle suspensions and dissolved printlets, with citrate coating mitigating hatching delays observed at higher concentrations. Altogether, these results demonstrate that combining iron oxide nanoparticles with FDM-based additive manufacturing enables the production of pharmaceutically relevant and customizable oral dosage forms with improved dissolution behavior and exhibiting low acute toxicity. This platform offers a proof-of-concept toward personalized iron supplementation therapies that address the limitations of conventional formulations.