ABSTRACT
Magnetic resonance imaging has become an essential tool in medicine for the investigation of physiological processes. The key issues related to contrast agents, i.e., substances that are injected in the body for imaging, are the efficient enhancement of contrast, their low toxicity, and their defined biodistribution. Polyurea nanocapsules containing the gadolinium complex Gadobutrol as a contrast agent in high local concentration and high relaxivity up to 40 s-1 mmol-1 L are described. A high concentration of the contrast agent inside the nanocapsules can be ensured by increasing the crystallinity in the shell of the nanocapsules. Nanocapsules from aliphatic polyurea are found to display higher crystallinity and higher relaxivity at an initial Gadobutrol concentration of 0.1 m than aromatic polyurea nanocapsules. The nanocapsules and the contrast agent are clearly identified in cells. After injection, the nanocarriers containing the contrast agent are mostly found in the liver and in the spleen, which allow for a significant contrast enhancement in magnetic resonance imaging.
Subject(s)
Contrast Media/administration & dosage , Magnetic Resonance Imaging , Nanocapsules/administration & dosage , Organometallic Compounds/administration & dosage , Animals , Contrast Media/chemistry , Dendrites/drug effects , Gadolinium/administration & dosage , Gadolinium/chemistry , Humans , Liver/diagnostic imaging , Liver/drug effects , Mesenchymal Stem Cells/drug effects , Mice , Nanocapsules/chemistry , Organometallic Compounds/chemistry , Polymers/chemistry , Spleen/diagnostic imaging , Spleen/drug effects , Tissue DistributionABSTRACT
The enhanced relaxation of hydrogen atoms of surrounding water from suitable contrast agent promotes magnetic resonance imaging as one of the most important medical diagnosis technique. The key challenge for the preparation of performant contrast agents for magnetic resonance imaging with high relaxivity is to ensure a high local concentration of contrast agent while allowing a contact between water and the contrast agent. Both requirements are answered by tailoring a semipermeable confinement for a gadolinium complex used as contrast agent. A locally high concentration is achieved by successfully encapsulating the complex in polymer nanocontainers that serves to protect and retain the complex inside a limited space. The access of water to the complex is achieved by carefully controlling the chemistry of the shell and the core of the nanocontainers. The confinement of the nanocontainers enables an increased relaxivity compared to an aqueous solution of the contrast agent. The nanocontainers are successfully applied in vivo to yield enhanced contrast in magnetic resonance imaging.
