POLYCHELATING AGENT INCORPORATION LIPOSOMES & MICELLES

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A novel polymeric probe capable of chelating multiple metal atoms (In, Gd) and suitable for the incorporation into liposomes and micelles will be synthesized and tested in vitro. A new molecule represents low-molecular- weight DTPA-polylysine linked via its N-terminus to a lipid anchor, NGPE-PE (DTPA-PLL-PE). In a preliminary experiment, we demonstrated here that liposomes containing 3 mole % of new membrane- bound polychelator and loaded with Gd possess enhanced relaxivity for water protons when compared with liposomes loaded with Gd via known membranotropic DTPA-SA and DTPA-PE. Liposomes will be prepared with variable contents of DTPA-PLL-PE and polyethylene glycol-PE (PEG-PE) and optimized in terms of their relaxivity and stability towards blood plasma. PED-PE-based micelles will be prepared containing variable quantities of DTPA-PLL-PE will be prepared. Their relaxivity and stability will be studied upon loading with Gadolinium. PROPOSED COMMERCIAL APPLICATIONS: Currently there are no vascular imaging agents marketed for Magnetic Resonance Imaging. There are 8 million cases of coronary artery disease per year of which there are one million scans estimated for this population. A MRI angiography contrast agent would have a large potential market in the USA alone.