Biocompatible magnetic gelatin nanoparticles with enhanced MRI contrast performance prepared by single-step desolvation method

Abstract

Magnetic nanoparticles are versatile materials that have boosted the development of different biomedical applications, being superparamagnetic magnetite nanoparticles a milestone in the field, after achieving clinical approval as contrast agents in magnetic resonance imaging (Feridex®), magnetic hyperthermia agents for oncological treatments (NanoTherm®), or iron deficiency supplement (Feraheme®). However, its potential as theragnostic agent could be further expanded by its encapsulation within a biodegradable hydrogel, capable of enhancing the biocompatibility and loading abilities, to simultaneously carry drugs, radiotracers, or biomolecules. Gelatin, is a natural biopolymer with optimal in vivo feature and gelling capacity that has been extensively used for decades in pharmaceuticals. In this work, we have addressed the preparation of gelatin nanoparticles, bare and loaded with magnetite nanoparticles, with controlled size to be used as contrast agents in magnetic resonance imaging. The main formulation parameters influencing the preparation of gelatin nanoparticles with controlled size by single-step desolvation method, were studied and optimized, to produce small gelatin nanoparticles (97nm) and highly loaded (38% w/w) Fe3O4@citrate gelatin nanoparticles (150 nm) with high magnetic response (65emus/g). The viability assays of the magnetic gelatin nanoparticles, tested with mesenchymal stem cells, showed negligible toxicity and in vitro magnetic resonance imaging tests, performed in agar phantoms, revealed a good contrast for T2 weighting MRI, r2 = 265.5(mM-1 s-1), superior to commercial products, such as Resovist or Endorem.