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Ultra-small size gelatin nanogel as a blood brain barrier impermeable contrast agent for magnetic resonance imaging
- Source :
- Acta biomaterialia. 125
- Publication Year :
- 2020
-
Abstract
- Magnetic Resonance Imaging (MRI) contrast agents with rapid renal excretion that do not penetrate the blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCFB) are preferred for safer and low-risk diagnosis. Gadolinium (Gd)-conjugated nanoparticles have been proposed for use as contrast agents; however, the particle size must range between 1 to 7 nm to ensure rapid renal excretion. In this study, three types of gelatin, dissolved in water at varying concentrations of 0.1-2 wt.%, were irradiated with 5 kGy γ-rays at 25°C under aerated conditions to produce ultra-small gelatin nanogels having an average particle size ranging between 6 ± 2 to 21 ± 4 nm. Ultra-small Gd-coordinated gelatin nanogels (GdGN) suitable for use as MRI contrast agents were produced using 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-NHS) and DOTA-butylamine as Gd ligand derivatives. Non-cytotoxicity and effective relaxivity of GdGN as a positive MRI contrast agent were verified using in vivo experiments. Rapid renal excretion of GdGN was observed in mice within 1 h with no accumulation in the liver. GdGN did not migrate across the BCFB in normal mice, thus emphasizing its safety as an MRI contrast agent. STATEMENT OF SIGNIFICANCE: The authors developed ultra-small sized gelatin nanogels as blood-brain-barrier impermeable contrast agents for magnetic resonance imaging (MRI). The authors used radiation crosslinking technique to ensure better integrity of the amino acids present in the gelatin nanogels while conjugating with gadolinium (Gd) to form gadolinium-coordinated gelatin nanogels (GdGN). The safety and efficacy of GdGN, as MRI contrast agents, were verified by in vivo studies. GdGN exhibited rapid renal excretion within 90 minutes and no passage across the barriers in the brain.
- Subjects :
- food.ingredient
Gadolinium
MRI contrast agent
0206 medical engineering
Biomedical Engineering
chemistry.chemical_element
Contrast Media
Nanogels
02 engineering and technology
Blood–brain barrier
Biochemistry
Gelatin
Biomaterials
Mice
food
In vivo
medicine
Animals
Molecular Biology
medicine.diagnostic_test
Magnetic resonance imaging
General Medicine
021001 nanoscience & nanotechnology
020601 biomedical engineering
Magnetic Resonance Imaging
medicine.anatomical_structure
chemistry
Blood-Brain Barrier
Renal physiology
0210 nano-technology
Biotechnology
Nanogel
Biomedical engineering
Subjects
Details
- ISSN :
- 18787568
- Volume :
- 125
- Database :
- OpenAIRE
- Journal :
- Acta biomaterialia
- Accession number :
- edsair.doi.dedup.....7142d52a7df3c5df1f44d6a16c515937