Gadolinium-chitosan nanoparticles as a novel contrast agent for potential use in clinical bowel-targeted MRI: a feasibility study in healthy rats.
BACKGROUND
MRI is of increasing importance in the diagnostic evaluation of gastrointestinal diseases, with depiction of mucosal enhancement obtained with conventional intravenous contrast. Routine clinical use of contrast agents has been carried out using intravenous injection for mucosal imaging. Contrast agents that specifically target the intestinal mucosa are therefore needed to improve clinical imaging of the mucosal surface.


OBJECTIVE
To synthesize a novel contrast agent for gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles and observe the absorption of the nanoparticles in the colon wall of healthy rats by MR imaging in vivo.


METHODS
A contrast agent was successfully synthesized by a modified emulsion coalescence method, and the resulting agents were characterized in detail by dynamic light-scattering spectroscopy and inductively coupled plasma emission spectroscopy. The cytotoxicity of Gd-chitosan nanoparticles was evaluated by an MTT assay. Gadolinium-chitosan (Gd@chitosan) nanoparticles were administered to the colon mucosa of healthy rats by rectal administration, and MRI scans in vivo were carried out with a 3.0 T imaging scanner at various time points.


RESULTS
The prepared Gd@chitosan nanoparticles were ~420 nm in diameter with a 74.4% Gd-DTPA content. The MTT assay indicated little cytotoxicity. MRI results showed that nanoparticles can be retained in both the stratum submucosum and epithelial cells of the colon for almost 80 min. Transmission electron microscopy images further revealed that Gd@chitosan nanoparticles were localized inside the mucosal cells or intercellular space, while tissue from Gd-DTPA aqueous solution administration showed nothing. Due to the infusion of Gd@chitosan nanoparticles, the MR signal intensity of colon mucosa increased from about 6% to 35%, and the contrast enhancement was highest at 20 min after administration.


CONCLUSIONS
Gd@chitosan nanoparticles with high Gd-DTPA content were successfully prepared for use as a novel MRI contrast agent. All results indicated that rectally administered Gd@chitosan nanoparticles have the potential for MRI diagnosis of colon mucosal disease.
Department of Radiology, Ren Ji Hospital, Shanghai Jiao Tong University Medical School, Shanghai, China.
Jie-Jun
JJ
Cheng
Jun
J
Zhu
Xiao-Sheng
XS
Liu
Dan-Nong
DN
He
Jian-Rong
JR
Xu
Lian-Ming
LM
Wu
Juan
J
Zhou
Qi
Q
Feng
D000285:Administration, Rectal; D000818:Animals; D002470:Cell Survival; D048271:Chitosan / Q000493:pharmacokinetics / Q000633:toxicity; D003106:Colon / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D003287:Contrast Media / Q000493:pharmacokinetics; D005240:Feasibility Studies; D019786:Gadolinium DTPA / Q000493:pharmacokinetics / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D003287:Contrast Media; D048271:Chitosan; D019786:Gadolinium DTPA