Abstract
Prostaglandin E1 (PGE1), a vasodilator and platelet aggregation inhibitor, effectively treats many diseases. However, PGE1 is generated locally and acts locally to regulate physiological responses, thereby suppressing the progress of disease. Therefore, the therapeutic use of PGE1 necessitates the targeting of specific sites to maximize local action and prevent systemic side effects. The authors have developed a PGE1 preparation, using lipid microspheres (LM) with a 0.2 μ diameter (o/w emulsion) as carriers for passive targeting of sites of vascular lesions ; the preparation is called lipo-PGE1. Favorable preclinical and clinical results have been achieved with preparation. The intravascular distribution of lipo-PGE1 injected intravenously in spontaneously hypertensive rats(SHR) was investigated using electron microscopy. LM were accumulated in the subendothelial space of vascular walls, particularly in vascular lesions associated with hypertension. Laser confocal imaging revealed the marked uptake of PGE1 by endothelial cells of diseased or newly developed vessels treated with lipo-PGE1. On the other hand, free PGE1 showed trace accumulation in the endothelial cells. The control cells incubated with normal mouse IgG instead of anti-PGE1 antibody did not show any fluorescence. Lipo-PGE1 is delivered preferentially to the site of vascular lesions, and PGE1 becomes less irritant because it is incorporated into the microspheres. In addition, its inactivation in the lungs is slightly reduced for the same reason. All these features of the preparation strongly suggest that it would be very valuable in clinical practices. We performed the Phase III clinical trial of lipo-PGE1 conducted in Japan which clearly showed that lipo-PGE1 is safe and effective in patients with arteriosclerotic vascular disease, diabetic neuropathy, peripheral vascular disease secondary to diffuse connective tissue diseases, vibration disease, or ductus arteriosusdependent congenital heart disease.
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