Jpn. J. Pharmacol. 81 (1), 107 - 114 (1999)

Vasodilating Effect and Tissue Accumulation of Prostaglandin E1
Incorporated in Lipid Microspheres on the Rat Ductus Arteriosus

Yukihiro Chino1, Toshiya Minagawa1, Yoshiro Kohno1, Kiyomi Fukushima1 and Kazuo Momma2

1Research Center, Taisho Pharmaceutical Co., Ltd., 1 - 403 Yoshino-cho, Ohmiya, Saitama 330 - 8530, Japan
2Department of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, 8 - 1 Kawada-cho Shinjuku-ku, Tokyo 162 - 0054, Japan

Abstract: Prostaglandin E1 incorporated in lipid microspheres (lipo PGE1) was administered to the umbilical vein of neonatal rats. Morphological measurement and quantitative autoradioluminography assessed the relationship between the vasodilating effect and tissue accumulation of lipo PGE1 in the ductus arteriosus. In the morphological measurement under microscopy, the inner diameter ratio of the ductus arteriosus to the main pulmonary artery after infusion of 3H-labeled lipo PGE1 (3H-lipo PGE1) continued to remain significantly higher than that of free 3H-PGE1. Autoradioluminography of the frozen frontal section of neonates after intravenous infusion of 3H-lipo PGE1 for 2 h revealed that the ductus levels of radioactivity were higher than those of free 3H-PGE1 in saline solution, although the blood levels were almost equal. Localization of lipo PGE1 labeled with a lipophilic fluorescent probe, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (diI), in the endothelial cells of the ductus arteriosus was confirmed by confocal laser scanning microscopy. These findings suggest that the incorporation of lipid microspheres by the endothelial cells is one of the mechanisms that enables lipo PGE1 to accumulate to higher levels in the ductus tissue and to act more efficiently than free PGE1 in neonatal rats.

Keywords: Prostaglandin E1, Lipid microsphere, Ductus arteriosus, Drug delivery,

Copyrightę The Japanese Pharmacological Society 1999

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