POLYCHELATING AGENT INCORPORATION LIPOSOMES & MICELLES

本文将合成一种新型聚合物探针，该探针能够螯合多个金属原子（In, Gd），并适用于脂质体和胶束的掺入。一个新分子代表低分子量dtpa -聚赖氨酸通过其n端连接到脂质锚点NGPE-PE （DTPA-PLL-PE）。在一项初步实验中，我们在这里证明了含有3mol %的新膜结合多螯合剂并装载Gd的脂质体与通过已知的膜性DTPA-SA和DTPA-PE装载Gd的脂质体相比，具有更强的水质子弛豫性。用不同含量的DTPA-PLL-PE和聚乙二醇- pe （PEG-PE）制备脂质体，并对其对血浆的弛缓性和稳定性进行优化。将制备含有不同数量的DTPA-PLL-PE的聚乙二醇-聚乙烯基胶束。它们的弛豫性和稳定性将在钆加载后进行研究。建议的商业应用：目前还没有用于磁共振成像的血管显像剂上市。每年有800万冠状动脉疾病病例其中估计有100万次扫描。MRI血管造影造影剂仅在美国就有很大的潜在市场。

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.