Abstract

Iron deficiency is the primary nutritional deficiency globally and iron dextran nanoparticles (IDN) are used for supplementation. Here we have applied theoretical, computational and experimental studies to understand the behavior of IDN and its interaction with a micrometric crosslinked gelatin scaffold (MCGS) to potentially develop a drug delivery system. Modeling single IDN reveals a complex network of interactions ranging from strong coordination bonds to weak van der Waals forces. Computational analyses reveal that multiple IDN (4 units) exhibit self-aggregation from 100 ns. In the presence of collagen (used to simulate MCGS), disaggregation occurs. The IDN-MCGS interactions are preferentially established (16–18 %) with the smaller/flexible amino acids alanine, proline and glycine. We hypothesize that the disaggregation of IDN in the presence of collagen is responsible for the low encapsulation efficiency (6.2–8.3 %) and low loading charge (1.9–3.7 %) during experimental encapsulation in MCGS (14–21 ?m). X-ray diffraction reveal the absence of new crystalline arrangements resulting from the IDN-MCGS formulation. This is the first time that theoretical, computational and experimental studies were applied to IDN, multiple IDN and interactions with MCGS. These tools could be used for other protein scaffolds to predict drug encapsulation and delivery. © 2025