Nebulized liposomal gadobenate dimeglumine contrast formulation for magnetic resonance imaging of larynx and trachea

Abstract

Xiaohui Wei1,2, Huawei Wu3, Qing Lu3, Jianrong Xu3, Yuhong Xu1,21School of Biomedical Engineering and Med-X Research Institute; 2School of Pharmacy, Shanghai Jiao Tong University; 3Department of Radiology, Renji Hospital affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: To develop a lipid-stabilized contrast formulation containing gadobenate dimeglumine for clear visualization of the mucosal surfaces of the larynx and trachea for early diagnosis of disease by magnetic resonance imaging.Methods: The contrast formulation was prepared by loading gadobenate dimeglumine into egg phosphotidylcholine, cholesterol, and sterylamine nanoliposomes using the dehydration-rehydration method. The liposomal contrast formulation was ultrasonically nebulized, and the deposition and coating pattern on explanted pig laryngeal and tracheal segments was examined by inductively coupled plasma atomic emission spectroscopy. The sizes of the nebulized droplets were characterized by photon correlation spectroscopy. The contrast-enhanced mucosal surface images of the larynx and trachea were obtained in a 3.0T magnetic resonance scanner using a T1-weighted spectral presaturation inversion recovery sequence.Results: Various cationic liposome formulations were compared for their stabilization effects on the droplets containing gadobenate dimeglumine. The liposomes composed of egg phosphotidylcholine, cholesterol, and sterylamine in a molar ratio of 1:1:1 were found to enable the most efficient nebulization and the resulting droplet sizes were narrowly distributed. They also resulted in the most even coating on the laryngeal and tracheal lumen surfaces and produced significant contrast enhancement along the mucosal surface. Such contrast enhancement could help clearer visualization of several disease states, such as intraluminal protrusions, submucosal nodules, and craters.Conclusion: This lipid-stabilized magnetic resonance imaging contrast formulation may be useful for improving mucosal surface visualization and early diagnosis of disease originating in the mucosal surfaces of the larynx and trachea.Keywords: lipid, gadolinium, magnetic resonance imaging, upper airway, nebulization, mucoadhesion