Marked hypotensive and blood flow-increasing effects of a new lipo-PGE1 (lipo-AS013) due to vascular wall targeting

被引：34

作者：

Igarashi, R ^{[1
]}

Takenaga, M ^{[1
]}

Takeuchi, J ^{[1
]}

Kitagawa, A ^{[1
]}

Matsumoto, K ^{[1
]}

Mizushima, Y ^{[1
]}

机构：

[1] St Marianna Med Univ, Sch Med, Inst Med Sci, Dept 2,Miyamae Ku, Kawasaki, Kanagawa 2168512, Japan

来源：

JOURNAL OF CONTROLLED RELEASE | 2001年 / 71卷 / 02期

关键词：

vascular wall targeting; prodrug of PGE(1); AS013; lipid microspheres (LM);

D O I：

10.1016/S0168-3659(00)00373-4

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Lipo-AS013 is being developed as an improved formulation of lipo-PGE,. which is widely used in clinical practice in Japan and some Asian countries. We have previously reported that lipo-AS013. which is a lipid microsphere (LM) preparation of a chemically stable and lipophilic PGE, prodrug (AS013. Fig. I). slowly releases small amounts of the active ingredient (AS013) in human plasma. In the present study. to estimate the vascular wall targeting ability and efficacy of lipo-AS013. we determined the hypotensive and blood Row-increasing effects of lipo-AS013. lipo-PGE(1). PGE(1)CD. and AS013. Lipo-AS013 was found to have longer-lasting hypotensive and blood Row-increasing effects than the other agents. The two LM preparations, lipo-PGE(1) and lipo-AS013, had a markedly stronger effect than PGE(1)CD and AS013 alone. demonstrating the benefit of drug delivery using LM. In spontaneously hypertensive rats (SHR). lipo-AS013 also had a significant hypotensive effect. To confirm vascular wall targeting by lipo-AS013. the localization of Pt;E, in the aorta and neovascular capillaries of rat was investigated by immunostaining. The results indicated that lipo-AS013 was more efficient at delivering the active ingredient (AS013) to the vessel wall. In conclusion, lipo-AS013 could supersede lipo-PGE, and PGE,CD in clinical use. (C) 2001 Elsevier Science B.V. All rights reserved.

引用

页码：157 / 164

页数：8

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