Abstract
Introduction: Liposomes are the most established nanocarriers that can be loaded with contrast agents as well as tailored for targeting to the desired tissue. Targeted CT liposomes represent a novel approach for rapid thrombus imaging. They allow specific and selective accumulation in thrombus providing significant contrast enhancement (expressed as HU) over the surrounding tissue. Hypothesis: We hypothesize that preparation technology will produce homogenous liposomes with sufficient level of loaded CT contrast agent. Methods: Liposomes were composed of distearoyl phosphatidylcholine, cholesterol, and distearoyl phosphatidylethanolamine - polyethylene glycol 2000 (molar ratio, 55/45/5). CT liposomes were prepared by lipid film hydration with iohexol (Omnipaque 350, GE Healthcare) followed by freeze-thaw extrusion (100 nm). Subsequently, they were purified by dialysis (Slide-A-Lyzer, cut-off 10 kDa) to remove un-loaded ioxehol. After purification, liposome-associated iohexol was determined by UV/VIS spectrophotometry and CT. Size distribution of final CT liposomes was assessed by dynamic light scattering. Results: Preparation technology produced homogenous liposome population having appropriate size distribution (90-110 nm and PD index, 0.05-0.10). Iohexol that remains associated in final CT liposomes represented only 5% of its initial level entering the preparation process. Almost 95% of iohexol was released and its final content was found to be 5 mg iodine/ml. Conclusions: Liposomal CT formulation was prepared with satisfactory size distribution and homogenity. Although the significant portion of iohexol was released, these CT liposomes were still detectable in vitro by CT. This basic liposomal platform will be optimized to achieve higher iohexol loading and will be further developed for thrombus imaging such as targeted CT liposomes.
Published Version
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