PARAMAGNETIC POLYMERIZED LIPOSOMES - SYNTHESIS, CHARACTERIZATION, ANDAPPLICATIONS FOR MAGNETIC-RESONANCE-IMAGING

Liposomes are biocompatible materials that show promise as vehicles fo r drug delivery, inhibitors of cell adhesion, and carriers for the int roduction of genetic material into cells. In this paper, we describe t he synthesis and characterization of a new class of polymerized liposo me particles (paramagnetic polymerized liposome (PPL), Figure 1) that have lanthanide ion chelates as head groups and that can be easily vis ualized using magnetic resonance imaging (MRI). The R(1) molar relaxiv ity was found to depend primarily on the linker length (m) and on the surface metal density and only weakly on particle size. PPLs containin g 10 mol % of compound 1b (m = 2) and 90 mol % of compound 3 had a R(1 ) = 12.2 mM(-1) s(-1), while PPLs with 10 mol % compound 1a (m = 1) an d 90 mol % of compound 3 had a R(1) = 5.7 mM(-1) s(-1). PPLs with 10 m ol % of compound 1a and 90 mol % of compound 4 had a R(1) = 8.9 mM(-1) s(-1), while PPLs with 50 mol % of compound 1a and 50 mol % of compou nd 4 had a R(1) = 4.3 mM(-1) s(-1). A biotinylated lipid (compound 2) was also incorporated into the particle without affecting R(1) relaxiv ities for use as a marker for histochemical studies. We have also for the first time used atomic force microscopy (AFM) to investigate the s ize and nature of these particles in an aqueous environment. We feel t hat these new materials may prove useful for the in vivo investigation of liposome formulations as vehicles for therapeutic applications and for evaluating tissue pathology with MRI.