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.
Highlights
The development of nanomaterials with designed abilities has witnessed an intense research in the last years
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
Optimization and characterization of gelatin nanoparticles (GNPs) by 1-step desolvation method Desolvation is a thermodynamically driven process for self-assembling polymers into nanoparticles, which depends on a large set of formulation parameters like polymer concentration, pH, amount of desolvating agent, concentration of crosslinking agent, and temperature
Summary
The development of nanomaterials with designed abilities has witnessed an intense research in the last years. Based on the control achieved at chemical level, the production of nanomaterials can be afforded combining hybrid inorganic/organic phases [1] and designed properties only observable at the nanoscale like enhanced selective catalytic/photocatalytic activities [2, 3], tailored plasmonic response [4], size-dependent fluorescence [5], or superparamagnetic (SPM) behaviour [6], among others This key-enabling technology is opening the door to a plethora of innovative applications that are permeating different fields from energy, spintronics, environmental remediation technologies to biotechnology or biomedicine. Nanobiomedicine benefits from the similarity of scales shared by nanoparticles (NPs) and relevant biological entities such as viruses, cells or bacteria. For this reason, the development of complex nanomaterials, that can be designed to interact locally with biological processes, has delivered new diagnostic and therapeutic paradigms and new tools. The general stability of these structures under different biological conditions (pH, pressure in blood stream, tissues stiffnesses, etc) highly depends on the use of an external surfactant coating which poses a challenge for in vivo applications [10]
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