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,
Autoradioluminography